Amino alcohol compounds

ABSTRACT

Amino alcohol compounds and phosphonic acid compounds having excellent immunosuppressive activity, pharmacologically acceptable salts thereof and pharmacologically acceptable esters thereof, and pharmaceutical compositions comprising such compounds, the compounds having the following formula: 
                         
wherein R 1  and R 2  each represent hydrogen, or a protecting group of the amino group; R 3  represents hydrogen, or a protecting group of the hydroxyl group; R 4  represents a lower alkyl group; n is 1 to 6; X represents oxygen or nitrogen, which is unsubstituted or substituted with a lower alkyl group; Y represents ethylene; Z represents a C 1 –C 10  alkylene; R 5  represents an aryl group; and R 6  and R 7  each represents hydrogen; provided that when R 5  represents hydrogen, then Z represents a group other than a single bond or a straight chain C 1 –C 10  alkylene group.

CROSS REFERENCE TO RELATED APPLICATION

This application is a continuation-in-part application of Internationalapplication PCT/JP03/00136 filed on Jan. 9, 2003, the entire contents ofwhich are incorporated by reference herein.

TECHNICAL FIELD

The present invention relates to amino alcohol derivatives or phosphonicacid derivatives having excellent immunosuppressive activity,pharmacologically-acceptable salts of amino alcohol derivatives orphosphonic acid derivatives, pharmacologically acceptable esters ofamino alcohol derivatives or phosphonic acid derivatives, and topharmaceutical compositions comprising said compounds as an activeingredient.

The present invention also relates to pharmaceutical compositionscomprising, as active ingredients, one or more immunosuppressants andone or more compounds selected from the group consisting of aminoalcohol derivatives or phosphonic acid derivatives having excellentimmunosuppressive activity, pharmacologically acceptable salts thereof,and pharmacologically acceptable esters thereof. Said compositions areuseful as preventive or therapeutic agents for autoimmune diseases suchas rejection of transplanted tissues or cells, rheumatoid arthritis, orother immune activity-related autoimmune diseases.

BACKGROUND OF THE INVENTION

In the past, anti-inflammatory agents such as steroids have been usedfor inflammatory reactions arising from abnormal immune response intreatment of immune-related diseases such as rheumatoid arthritis andother autoimmune diseases. These are, however, a symptomatic therapy,but not a fundamental remedy.

Furthermore, it has been reported that immune system abnormalities arealso involved in the development of diabetes and nephritis, but agentsthat improve these abnormalities have not yet been developed.

On the other hand, it is critical to develop an approach to suppress theimmune response for avoiding rejection in transplanted tissues or cells,as well as for treating and preventing various autoimmune diseases.

However, immunosuppressants, such as cyclosporin A (CsA) and tacrolimus(TRL) that have been known in the past, are known to show toxicityagainst the kidney and liver. Although treatments that also use steroidsare commonly used for the relief of such adverse reactions, it ispresently the case that such agents have not necessarily led toproducing a satisfactory immunosuppressive effect without showing anyadverse reaction.

In light of this background, it has been attempted to find excellentcompounds with immunosuppressive effects that are less toxic.

As to immunosuppressants, the following compounds are known.

(1) Compounds Having the General Formula (a) Disclosed in WO 94/08943(Page 371)

{in the above compounds (a),

R_(x) represents a straight or branched carbon chain which mayoptionally be substituted with one or more substituents [said chain maycontain a double bond, a triple bond, an oxygen atom, a sulfur atom, agroup of formula —N(R_(x) ⁶)— (wherein R_(x) ⁶ represents a hydrogenatom), an arylene group which may optionally be substituted with one ormore substituents, or a heteroarylene group which may optionally besubstituted with one or more substituents, and may contain, at the endof said chain, an aryl group which may optionally be substituted withone or more substituents, a cycloalkyl group which may optionally besubstituted with one or more substituents, or an aromatic heterocyclicgroup which may optionally be substituted with one or moresubstituents], and

R_(x) ², R_(x) ³, R_(x) ⁴, and R_(x) ⁵ are the same or different andeach represents a hydrogen atom or an alkyl group] are known asimmunosuppressants.

The above compounds (a) of the prior art contain two oxymethyl groups(—CH₂OR_(x) ⁴ and —CH₂OR_(x) ⁵) as essential groups substituted on thesame carbon atom. The compounds of the present invention, however,contain one —CH₂OR³ group and one lower alkyl group as essential groupssubstituted on the same carbon atom and are different from the compounds(a) in these substituents.

(2) Compounds Having the General Formula (b) Disclosed in WO 96/06068(Page 271)

[in the above compounds (b),

R_(y) ¹, R_(y) ², and R_(y) ³ each represent a hydrogen atom or thelike, W represents a hydrogen atom, an alkyl group or the like, Z_(y)represents a single bond or an alkylene group, X_(y) represents ahydrogen atom or an alkoxy group, and Y_(y) represents a hydrogen atom,an alkyl, alkoxy, acyl, acyloxy, amino, acylamino group or the like] areknown as immunosuppressants.

The above compounds (b) contain a phenyl group as an essential group inthe basic skeleton. The compounds of the present invention contain aheterocyclic group such as a furyl group, a pyrrolyl group, or apyrrolyl group having a substituent on the nitrogen atom instead of thephenyl group of compounds (b) and are different from the compounds (b).

However, compounds having a similar chemical structure to compounds (I)of the present invention have heretofore not been disclosed concretelyin that publication.

(3) Compounds Having the General Formula (c) Disclosed in WO 98/45249

[in the above compounds (c),

R_(z) ¹, R_(z) ², R_(z) ³, and R_(z) ⁴ are the same or different andeach represents a hydrogen atom or an acyl group] are known asimmunosuppressants.

The above compounds (c) contain two oxymethyl groups (—CH₂OR_(z) ³ and—CH₂OR_(z) ⁴) as essential groups substituted on the same carbon atom.The compounds of the present invention, however, contain one —CH₂OR³group and one lower alkyl group as essential groups substituted on thesame carbon atom and are different from the compounds (c) in thesesubstituents.

In addition, above compounds (c) contain a phenyl group between the—(CH₂)₂— group and the —CO—(CH₂)₄ group as an essential group in thebasic skeleton. The compounds of the present invention contain aheterocyclic group such as a furyl group, a pyrrolyl group, or apyrrolyl group having a substituent on the nitrogen atom instead of thephenyl group of compound (c) and are different from the compounds (c).

On the other hand, a compound having the general formula (II) of thepresent invention shown below wherein X represents a sulfur atom isdisclosed in WO 02/06268 as a compound wherein the protecting group ofthe hydroxyl group is a residual group of an ester of phosphoric acid.

Furthermore, as to combinations of immunosuppressants, combinations ofimmunosuppressants such as FTY-720 and cyclosporin A or FTY-720 andtacrolimus are disclosed in Japanese Patent Publication (Kokai) NumberHei 11-80026.

In light of this background, it has been desired to find excellentpharmaceutical compositions with immunosuppressive effects that are lesstoxic.

SUMMARY OF THE INVENTION

The present inventors have eagerly studied new compounds havingexcellent immunosuppressive activity with low toxicity and found newcompounds which are useful as preventive or therapeutic agents forautoimmune diseases or other immunology-related diseases such asrejection caused by transplantation of various organs or skin, systemiclupus erythematosus, rheumatoid arthritis, polymyositis, fibrositis,skeletal muscle inflammation, arthrosteitis, osteoarthritis,dermatomyositis, scleoderma, Behcet's syndrome, Crohn's disease,ulcerative colitis, autoimmune hepatitis, aplastic anemia, idiopathicthrombocytopenic purpura, autoimmune hemolytic anemia, multiplesclerosis, autoimmune bullosis, psoriasis vulgaris, vasculitis syndrome,Wegener's granuloma, uveitis, Sjogren's syndrome, idiopathicinterstitial pneumonia, Goodpasture's syndrome, sarcoidosis, allergicgranulomatous angitis, bronchial asthma, myocarditis, cardiomyopathy,aortitis syndrome, post myocardial infartion syndrome, primary pulmonaryhypertension, minimal change nephrotic syndrome, membranous nephropathy,membranoproliferative glomerulonephritis, focal glomerular sclerosis,crescentic glomerulonephritis, myasthenia gravis, inflammatoryneuropathy, atopic dermatitis, chronic actinic dermatitis,photosensitivity, pressure sores, Sydenham's chorea, sclerosis,adult-onset type diabetes mellitus, insulin dependent diabetes mellitus,juvenile diabetes mellitus, atherosclerosis, glomerular nephritis, IgAnephropathy, tubulointerstitial nephritis, primary biliary cirrhosis,primary sclerosing cholangitis, fulminant hepatitis, viral hepatitis,GVHD, contact dermatitis, and sepsis; diseases of infection by fungus,mycoplasma, virus, and protozoan and the like; cardiovascular diseasessuch as cardiac failure, cardiac hypertrophy, arrhythmia, anginapectoris, cardiac ischemia, arterial embolism, aneurysm, varix, andcirculation disorders; brain diseases such as Alzheimer's disease,dementia, Parkinson's disease, stroke, brain infarction, brain ischemia,depression, manic-depressive illness, schizophrenia, Huntington'schorea, epilepsy, convulsion, attention deficit disorder, encephalitis,cerebral meningitis, loss of appetite, and hyperphagia; and variousdiseases such as lymphoma, leukemia, diuresis, pollakisuria, anddiabetic retinopathy (particularly, autoimmune diseases such asrejection caused by transplantation of various organs or skin, systemiclupus erythematosus, rhematoid arthritis, multiple sclerosis, and atopicdermatitis), and completed the present invention.

Furthermore, the present inventors have studied eagerly pharmaceuticalcompositions having immunosuppressive activity and found that thepharmaceutical compositions of the present invention comprising, asactive ingredients, one or more immunosuppressants and one or morecompounds of the present invention exhibit excellent immunosuppressiveactivity with low toxicity. The pharmaceutical compositions increaseactivity more than that of the individual immunosuppressants anddecrease adverse reactions so that they are less than that of theindividual immunosuppressants. As a result, the pharmaceuticalcompositions of the present invention are useful as preventive ortherapeutic agents for autoimmune diseases or other immunology-relateddiseases such as rejection caused by transplantation of various organsor skin, systemic lupus erythematosus, rheumatoid arthritis,polymyositis, fibrositis, skeletal muscle inflammation, arthrosteitis.,osteoarthritis, dermatomyositis, scleoderma, Behcet's syndrome, Crohn'sdisease, ulcerative colitis, autoimmune hepatitis, aplastic anemia,idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia,multiple sclerosis, autoimmune bullosis, psoriasis vulgaris, vasculitissyndrome, Wegener's granuloma, uveitis, Sjogren's syndrome, idiopathicinterstitial pneumonia, Goodpasture's syndrome, sarcoidosis, allergicgranulomatous angitis, bronchial asthma, myocarditis, cardiomyopathy,aortitis syndrome, post myocardial infarction syndrome, primarypulmonary hypertension, minimal change nephrotic syndrome, membranousnephropathy, membranoproliferative glomerulonephritis, focal glomerularsclerosis, crescentic glomerulonephritis, myasthenia gravis,inflammatory neuropathy, atopic dermatitis, chronic actinic dermatitis,photosensitivity, pressure sores. Sydenham's chorea, sclerosis,adult-onset type diabetes mellitus, insulin dependent diabetes mellitus,juvenile diabetes mellitus, atherosclerosis, glomerular nephritis, IgAnephropathy, tubulointerstitial nephritis, primary biliary cirrhosis,primary sclerosing cholangitis, fulminant hepatitis, viral hepatitis,GVHD, contact dermatitis, and sepsis; diseases of infection by fungus,mycoplasma, virus, and protozoan and the like; cardiovascular diseasessuch as cardiac failure, cardiac hypertrophy, arrhythmia, anginapectoris, cardiac ischemia, arterial embolism, aneurysm, varix, andcirculation disorders; brain diseases such as Alzheimer's disease,dementia, Parkinson's disease, stroke, brain infarction, brain ischemia,depression, manic-depressive illness, schizophrenia, Huntington'schorea, epilepsy, convulsion, attention deficit disorder, encephalitis,cerebral meningitis, loss of appetite, and hyperphagia; and variousdiseases such as lymphoma, leukemia, diuresis, pollakisuria, anddiabetic retinopathy (particularly, autoimmune diseases such asrejection caused by transplantation of various organs or skin, systemiclupus erythematosus, rhematoid arthritis, multiple sclerosis, and atopicdermatitis) and the present inventors completed the present invention.

The present invention is explained in detail.

-   (1) Amino alcohol derivatives of the present invention are compounds    of the general formula (I) shown below:

[wherein,

-   -   R¹ and R² are the same or different and each represents a        hydrogen atom, a lower alkyl group, or a protecting group of the        amino group;    -   R³ represents a hydrogen atom, a lower alkyl group, or a        protecting group of the hydroxyl group;    -   R⁴ represents a lower alkyl group;    -   n represents an integer of from 1 to 6;    -   X represents an oxygen atom or a group of formula ═N—D (wherein        D represents a hydrogen atom, a C₆–C₁₀ aryl group, a lower        alkylsulfonyl group, a C₆–C₁₀ arylsulfonyl group, or a group        selected from Substituent group (a));    -   Y represents an ethylene group, a vinylene group, an ethynylene        group, a group of formula: —E—CH₂— (wherein E represents a        carbonyl group or a group of formula: —CH(OH)—), a C₆–C₁₀        arylene group, or a C₆–C₁₀ arylene group substituted with from 1        to 3 substituents selected from Substituent group (a);    -   Z represents a single bond, a C₁–C₁₀ alkylene group, a C₁–C₁₀        alkylene group substituted with from 1 to 3 substituents        selected from Substituent group (a) and Substituent group (b), a        C₁–C₁₀ alkylene group which has an oxygen atom or a sulfur atom        in said carbon chain or at the end of said carbon chain, or a        C₁–C₁₀ alkylene group substituted with from 1 to 3 substituents        selected from the group consisting of Substituent group (a) and        Substituent group (b) which has an oxygen atom or a sulfur atom        in said carbon chain or at the end of said carbon chain;    -   R⁵ represents a hydrogen atom, a C₃–C₁₀ cycloalkyl group, a        C₆–C₁₀ aryl group, a 5- to 7-membered heterocyclic group        containing from 1 to 3 heteroatoms selected from the group        consisting of a sulfur atom, an oxygen atom, and a nitrogen        atom, a C₃–C₁₀ cycloalkyl group substituted with from 1 to 3        substituents selected from the group consisting of Substituent        group (a) and Substituent group (b), a C₆–C₁₀ aryl group        substituted with from 1 to 3 substituents selected from the        group consisting of Substituent group (a) and Substituent group        (b), or a 5- to 7-membered heterocyclic group containing from 1        to 3 heteroatoms selected from the group consisting of a sulfur        atom, an oxygen atom, and a nitrogen atom in which said        heterocyclic group is substituted with from 1 to 3 substituents        selected from Substituent group (a) and Substituent group (b);    -   R⁶ and R⁷ are the same or different and each represents a        hydrogen atom or a group selected from Substituent group (a);    -   Substituent group (a) represents the group consisting of a        halogen atom, a lower alkyl group, a halogeno lower alkyl group,        a lower alkoxy group, a lower alkylthio group, a carboxyl group,        a lower alkoxycarbonyl group, a hydroxyl group, a lower        aliphatic acyl group, an amino group, a mono-lower alkylamino        group, a di-lower alkylamino group, a lower aliphatic acylamino        group, a cyano group, and a nitro group; and    -   Substituent group (b) represents the group consisting of a        C₃–C₁₀ cycloalkyl group, a C₆–C₁₀ aryl group, a 5- to 7-membered        heterocyclic group containing from 1 to 3 heteroatoms selected        from the group consisting of a sulfur atom, an oxygen atom, and        a nitrogen atom, a C₃–C₁₀ cycloalkyl group substituted with from        1 to 3 substituents selected from Substituent group (a), a        C₆–C₁₀ aryl group substituted with from 1 to 3 substituents        selected from Substituent group (a), and a 5- to 7-membered        heterocyclic group containing from 1 to 3 heteroatoms selected        from the group consisting of a sulfur atom, an oxygen atom, and        a nitrogen atom in which said heterocyclic group is substituted        with from 1 to 3 substituents selected from Substituent group        (a);        provided that when R⁵ represents a hydrogen atom, then Z        represents a branched chain C₁–C₁₀ alkylene group, a C₁–C₁₀        alkylene group substituted with from 1 to 3 substituents        selected from the group consisting of Substituent group (a) and        Substituent group (b), a C₁–C₁₀ alkylene group which has an        oxygen atom or a sulfur atom in said carbon chain or at the end        of said carbon chain, or a C₁–C₁₀ alkylene group substituted        with from 1 to 3 substituents selected from the group consisting        of Substituent group (a) and Substituent group (b) which has an        oxygen atom or a sulfur atom in said carbon chain or at the end        of said carbon chain].

The present invention provides compounds of formula (I),pharmacologically acceptable salts thereof, and pharmacologicallyacceptable esters thereof.

Of these, preferred compounds are:

-   (2) a compound according to (1) wherein said compound of formula (I)    has the formula (Ia):

(wherein, R¹, R², R³, R⁴, R⁵, R⁶, R⁷, X, Y, Z and n have the samemeanings as those indicated hereinbefore), a pharmacologicallyacceptable salt thereof, or a pharmacologically acceptable esterthereof,

-   (3) a compound according to (1) wherein said compound of formula (I)    has the formula (Ib):

(wherein, R¹, R², R³, R⁴, R⁵, R⁶, R⁷, X, Y, Z and n have the samemeanings as those indicated hereinbefore), a pharmacologicallyacceptable salt thereof, or a pharmacologically acceptable esterthereof,

-   (4) a pharmacologically acceptable ester of the compound of    formula (I) according to (1) wherein said compound of formula (I)    has the formula (II):

(wherein, R¹, R², R⁴, R⁵, R⁶, R⁷, X, Y, Z and n have the same meaningsas those indicated hereinbefore; R¹⁰ and R¹¹ are the same or differentand each represents a hydrogen atom or a protecting group of phosphoricacid), or a pharmacologically acceptable salt thereof,

-   (5) a pharmacologically acceptable ester of the compound of    formula (II) according to (4) wherein said ester of formula (II) has    the formula (IIa):

(wherein, R¹, R², R⁴, R⁵, R⁶, R⁷, X, Y, Z and n have the same meaningsas those indicated hereinbefore; R¹⁰ and R¹¹ are the same or differentand each represents a hydrogen atom or a protecting group of phosphoricacid), or a pharmacologically acceptable salt thereof, and

-   (6) a pharmacologically acceptable ester of the compound of    formula (II) according to (4) wherein said ester of formula (II) has    the formula (IIb):

(wherein, R¹, R², R⁴, R⁵, R⁶, R⁷, X, Y, Z and n have the same meaningsas those indicated hereinbefore; R¹⁰ and R¹¹ are the same or differentand each represents a hydrogen atom or a protecting group of phosphoricacid), or a pharmacologically acceptable salt thereof.

-   (7) Phosphonic acid derivatives of the present invention are    compounds of the general formula (III) shown below:

(wherein, R¹, R², R⁴, R⁵, R⁶ R⁷, R¹⁰, R¹¹, X, Y, Z and n have the samemeanings as those indicated hereinbefore).

The present invention provides compounds of formula (III),pharmacologically acceptable salts thereof, and pharmacologicallyacceptable esters thereof.

Of these, preferred compounds are:

-   (8) a compound according to (7) wherein said compound of    formula (III) has the formula (IIIa):

(wherein, R¹, R², R⁴, R⁵, R⁶, R⁷, R¹⁰, R¹¹, X, Y, Z and n have the samemeanings as those indicated hereinbefore), a pharmacologicallyacceptable salt thereof, or a pharmacologically acceptable esterthereof, and

-   (9) a compound according to (7) wherein said compound of    formula (III) has the formula (IIIb):

(wherein, R¹, R², R⁴, R⁵, R⁶, R⁷, R¹⁰, R¹¹, X, Y, Z and n have the samemeanings as those indicated hereinbefore), a pharmacologicallyacceptable salt thereof, or a pharmacologically acceptable esterthereof.

DETAILED DESCRIPTION OF THE INVENTION

Of these, preferred compounds are:

-   (10) a compound according to any one of (1) to (9) wherein R¹ and R²    are the same or different and each represents a hydrogen atom, a    lower aliphatic acyl group, a lower alkoxycarbonyl group, an    aralkyloxycarbonyl group, or an aralkyloxycarbonyl group substituted    with from 1 to 3 substituents selected from Substituent group (a),    or a pharmacologically acceptable salt thereof,-   (11) a compound according to any one of (1) to (9) wherein R¹ and R²    are the same or different and each represents a hydrogen atom, a    lower aliphatic acyl group, or a lower alkoxycarbonyl group, or a    pharmacologically acceptable salt thereof,-   (12) a compound according to any one of (1) to (9) wherein R¹ and R²    are the same or different and each represents a hydrogen atom, a    C₁–C₄ aliphatic acyl group, or a C₁–C₄ alkoxycarbonyl group, or a    pharmacologically acceptable salt thereof,-   (13) a compound according to any one of (1) to (9) wherein R¹ and R²    are the same or different and each represents a hydrogen atom, a    C₁–C₂ aliphatic acyl group, or a C₁–C₂ alkoxycarbonyl group, or a    pharmacologically acceptable salt thereof,-   (14) a compound according to any one of (1) to (9) wherein R¹ and R²    are the same or different and each represents a hydrogen atom, an    acetyl group, or a methoxycarbonyl group, or a pharmacologically    acceptable salt thereof,-   (15) a compound according to any one of (1) to (9) wherein each of    R¹ and R² represents a hydrogen atom, or a pharmacologically    acceptable salt thereof,-   (16) a compound according to any one of (1) to (3) and (10) to (15)    wherein R³ represents a hydrogen atom, a lower alkyl group, a lower    aliphatic acyl group, an aromatic acyl group, an aromatic acyl group    substituted with from 1 to 3 substituents selected from Substituent    group (a), or a silyl group, or a pharmacologically acceptable salt    thereof,-   (17) a compound according to any one of (1) to (3) and (10) to (15)    wherein R³ represents a hydrogen atom or a lower alkyl group, or a    pharmacologically acceptable salt thereof,-   (18) a compound according to any one of (1) to (3) and (10) to (15)    wherein R³ represents a hydrogen atom or a C₁–C₄ alkyl group, or a    pharmacologically acceptable salt thereof,-   (19) a compound according to any one of (1) to (3) and (10) to (15)    wherein R³ represents a hydrogen atom, a methyl group, or an ethyl    group, or a pharmacologically acceptable salt thereof,-   (20) a compound according to any one of (1) to (3) and (10) to (15)    wherein R³ represents a hydrogen atom, or a pharmacologically    acceptable salt thereof,-   (21) a compound according to any one of (1) to (20) wherein R⁴    represents a C₁–C₄ alkyl group, or a pharmacologically acceptable    salt thereof,-   (22) a compound according to any one of (1) to (20) wherein R⁴    represents a C₁–C₂ alkyl group, or a pharmacologically acceptable    salt thereof,-   (23) a compound according to any one of (1) to (20) wherein R⁴    represents a methyl group, or a pharmacologically acceptable salt    thereof,-   (24) a compound according to any one of (1) to (23) wherein n    represents an integer 2 or 3, or a pharmacologically acceptable salt    thereof,-   (25) a compound according to any one of (1) to (23) wherein n    represents an integer 2, or a pharmacologically acceptable salt    thereof,-   (26) a compound according to any one of (1) to (25) wherein X    represents an oxygen atom, or a pharmacologically acceptable salt    thereof,-   (27) a compound according to any one of (1) to (25) wherein X    represents a group of formula: ═N—D (wherein D represents a hydrogen    atom, a C₁–C₄ alkyl group, or a phenyl group), or a    pharmacologically acceptable salt thereof,-   (28) a compound according to any one of (1) to (25) wherein X    represents a group of formula: ═N—CH₃, or a pharmacologically    acceptable salt thereof,-   (29) a compound according to any one of (1) to (28) wherein Y    represents an ethylene group, an ethynylene group, a group of    formula: —CO—CH₂—, a group of formula: —CH(OH)—CH₂—, a phenylene    group, or a phenylene group substituted with from 1 to 3    substituents selected from the group consisting of a halogen atom    and a lower alkyl group, or a pharmacologically acceptable salt    thereof,-   (30) a compound according to any one of (1) to (28) wherein Y    represents an ethylene group, an ethynylene group, a group of    formula: —CO—CH₂—, or a phenylene group, or a pharmacologically    acceptable salt thereof,-   (31) a compound according to any one of (1) to (30) wherein Z    represents a C₁–C₁₀ alkylene group or a C₁–C₁₀ alkylene group    substituted with from 1 to 3 substituents selected from the group    consisting of Substituent group (a) and Substituent group (b), or a    pharmacologically acceptable salt thereof,-   (32) a compound according to any one of (1) to (30) wherein Z    represents a C₁–C₆ alkylene group or a C₁–C₆ alkylene group    substituted with from 1 to 3 hydroxyl groups, or a pharmacologically    acceptable salt thereof,-   (33) a compound according to any one of (1) to (30) wherein Z    represents a C₁–C₅ alkylene group or a C₁–C₅ alkylene group    substituted with from 1 to 3 hydroxyl groups, or a pharmacologically    acceptable salt thereof,-   (34) a compound according to any one of (1) to (30) wherein Z    represents an ethylene group, a trimethylene group, a tetramethylene    group, or an ethylene, trimethylene, or tetramethylene group    substituted with one hydroxyl group, or a pharmacologically    acceptable salt thereof,-   (35) a compound according to any one of (1) to (30) wherein Z    represents an ethylene group, a trimethylene group, or a    tetramethylene group, or a pharmacologically acceptable salt    thereof,-   (36) a compound according to any one of (1) to (30) wherein Z    represents an ethylene group or a trimethylene group, or a    pharmacologically acceptable salt thereof,-   (37) a compound according to any one of (1) to (30) wherein Z    represents a C₁–C₁₀ alkylene group which has an oxygen atom or a    sulfur atom in said carbon chain or at the end of said carbon chain    or a C₁–C₁₀ alkylene group substituted with one substituent which    has an oxygen atom or a sulfur atom in said carbon chain or at the    end of said carbon chain (said substituent is selected from the    group consisting of a lower alkyl group and a hydroxyl group), or a    pharmacologically acceptable salt thereof,-   (38) a compound according to any one of (1) to (30) wherein Z    represents a C₁–C₁₀ alkylene group which has an oxygen atom or a    sulfur atom in said carbon chain or at the end of said carbon chain,    or a pharmacologically acceptable salt thereof,-   (39) a compound according to any one of (1) to (30) wherein Z    represents a C₁–C₁₀ alkylene group which has an oxygen atom in said    carbon chain or at the end of said carbon chain, or a    pharmacologically acceptable salt thereof,-   (40) a compound according to any one of (1) to (30) wherein Z    represents a C₁–C₆ alkylene group which has an oxygen atom in said    carbon chain or at the end of said carbon chain, or a    pharmacologically acceptable salt thereof,-   (41) a compound according to any one of (1) to (30) wherein Z    represents a group of formula —O—CH₂—, —O—(CH₂)₂—, —O—(CH₂)₃—,    —CH₂—O—, —(CH₂)₂—O—, or —(CH₂)₃—O—, or a pharmacologically    acceptable salt thereof,-   (42) a compound according to any one of (1) to (30) wherein Z    represents a group of formula —CH₂—O— or —(CH₂)₂ O—, or a    pharmacologically acceptable salt thereof,-   (43) a compound according to any one of (1) to (42) wherein R⁵    represents a hydrogen atom, or a pharmacologically acceptable salt    thereof,-   (44) a compound according to any one of (1) to (42) wherein R⁵    represents a C₃–C₁₀ cycloalkyl group, a C₆–C₁₀ aryl group, or a    C₃–C₁₀ cycloalkyl or C₆–C₁₀ aryl group substituted with from 1 to 3    substituents selected from the group consisting of a halogen atom, a    lower alkyl group, a halogeno lower alkyl group, a lower alkoxy    group, and a lower alkylthio group, or a pharmacologically    acceptable salt thereof,-   (45) a compound according to any one of (1) to (42) wherein R⁵    represents a C₃–C₁₀ cycloalkyl group, a C₆–C₁₀ aryl group, or a    C₃–C₁₀ cycloalkyl or C₆–C₁₀ aryl group substituted with from 1 to 3    substituents selected from the group consisting of a halogen atom, a    lower alkyl group, a halogeno lower alkyl group, and a lower alkoxy    group, or a pharmacologically acceptable salt thereof,-   (46) a compound according to any one of (1) to (42) wherein R⁵    represents a C₅–C₆ cycloalkyl group, a phenyl group, or a naphthyl    group, or a pharmacologically acceptable salt thereof,-   (47) a compound according to any one of (1) to (42) wherein R⁵    represents a cyclohexyl group or a phenyl group, or a    pharmacologically acceptable salt thereof,-   (48) a compound according to any one of (1) to (47) wherein R⁶ and    R⁷ are the same or different and each represents a hydrogen atom, a    halogen atom, a lower alkyl group, a halogeno lower alkyl group, a    lower alkoxy group, or a lower alkylthio group, or a    pharmacologically acceptable salt thereof,-   (49) a compound according to any one of (1) to (47) wherein each of    R⁶ and R⁷ represents a hydrogen atom, or a pharmacologically    acceptable salt thereof,-   (50) a compound according to any one of (4) to (15) and (21) to (49)    wherein R¹⁰ and R¹¹ are the same or different and each represents a    hydrogen atom or a lower alkyl group, or a pharmacologically    acceptable salt thereof,-   (51) a compound according to any one of (4) to (15) and (21) to (49)    wherein R¹⁰ and R¹¹ are the same or different and each represents a    hydrogen atom or a C₁–C₄ alkyl group, or a pharmacologically    acceptable salt thereof,-   (52) a compound according to any one of (4) to (15) and (21) to (49)    wherein R¹⁰ and R¹¹ are the same or different and each represents a    hydrogen atom, a methyl group, or an ethyl group, or a    pharmacologically acceptable salt thereof, and-   (53) a compound according to any one of (4) to (15) and (21) to (49)    wherein each of R¹⁰ and R¹¹ represents a hydrogen atom, or a    pharmacologically acceptable salt thereof.

Compounds according to (1) above which comprise any combination selectedfreely from the groups consisting of (2) and (3); (10) to (15); (16) to(20); (21) to (23); (24) and (25); (26) to (28); (29) and (30); (31) to(42); (43) to (47); and (48) and (49) are preferred.

Compounds according to (4) above which comprise any combination selectedfreely from the groups consisting of (5) and (6); (10) to (15); (21) to(23); (24) and (25); (26) to (28); (29) and (30); (31) to (42); (43) to(47); (48) and (49); and (50) to (53) are preferred.

Compounds according to (7) above which comprise any combination selectedfreely from the groups consisting of (8) and (9); (10) to (15); (21) to(23); (24) and (25); (26) to (28); (29) and (30); (31) to (42); (43) to(47); (48) and (49); and (50) to (53) are preferred.

Of these, the most preferred compounds are:

-   (54) a compound selected from the following compounds, a    pharmacologically acceptable salt thereof, or a pharmacologically    acceptable ester thereof:-   2-amino-2-methyl-4-[5-(5-phenylpentyl)furan-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)furan-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)furan-2-yl]butan-1-ol,    and-   2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]furan-2-yl}butan-1-ol,-   (55) a compound selected from the following compounds, a    pharmacologically acceptable salt thereof, or a pharmacologically    acceptable ester thereof:-   2-amino-2-methyl-4-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]butan-1-ol,-   2-amino-2-methyl-4-{1-methyl-5-[3-(4-methylphenoxy)prop-1-ynyl]pyrrol-2-yl}butan-1-ol,-   2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexyloxybut-1-ynyl)pyrrol-2-yl]butan-1-ol,-   2-amino-2-methyl-4-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]pyrrol-2-yl}butan-1-ol,-   2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[1-methyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[1-methyl-5-(4-phenylbutanoyl)pyrrol-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]butan-1-ol,-   2-amino-2-methyl-4-(1-methyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol,-   2-amino-2-methyl-4-[1-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[1-ethyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[1-ethyl-5-(4-phenylbutanoyl)pyrrol-2-yl]butan-1-ol,    and-   2-amino-2-methyl-4-[1-ethyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]butan-1-ol,-   2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol,-   2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol,-   2-amino-2-methyl-4-{1-(methyl-5-[4-(3-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol,-   2-amino-2-methyl-4-({-methyl-5-[4-(4-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol,-   2-amino-2-methyl-4-{1-methyl-5-[4-(4-methoxyphenyl)butanoyl]pyrrol-2-yl}butan-1-ol,-   2-amino-2-methyl-4-{1-methyl-5-[4-(3-methylphenyl)butyl]pyrrol-2-yl}butan-1-ol,-   2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol,-   2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol,-   2-amino-2-methyl-4-{1-methyl-5-[4-(3-trifluoromethylphenyl)butyl]pyrrol-2-yl}butan-1-ol.-   (56) a compound according to (4) wherein said compound is selected    from the following compounds or a pharmacologically acceptable salt    thereof:-   mono 2-amino-2-methyl-4-[5-(5-phenylpentyl)furan-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]-1-butyl    phosphate,-   mono 2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)furan-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)furan-2-yl]-1-butyl    phosphate, and-   mono    2-amino-2-methyl-4-(5-[3-(3,4-dimethylphenoxy)prop-1-ynyl)furan-2-yl)-1-butyl    phosphate,-   (57) a compound according to (4) wherein said compound is selected    from the following compounds or a pharmacologically acceptable salt    thereof:-   mono    2-amino-2-methyl-4-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{1-methyl-5-[3-(4-methylphenoxy)prop-1-ynyl]pyrrol-2-yl}-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexyloxybut-1-ynyl)pyrrol-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]pyrrol-2-yl}-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[1-methyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[1-methyl-5-(4-phenylbutanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{1-methyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2-yl}-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[1-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[1-ethyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[1-ethyl-5-(4-phenylbutanoyl)pyrrol-2-yl]-1-butyl    phosphate, and-   mono    2-amino-2-methyl-4-[1-ethyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butanoyl]pyrrol-2-yl}-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butanoyl]pyrrol-2-yl}-1-butyl    phosphate. (58) a compound according to (7) wherein said compound is    selected from the following compounds or a pharmacologically    acceptable salt thereof:-   3-amino-3-methyl-5-[5-(5-phenylpentyl)furan-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[5-(5-phenylpent-1-ynyl)furan-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[5-(5-cyclohexylpentanoyl)furan-2-yl]pentylphosphonic    acid, and-   3-amino-3-methyl-5-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]furan-2-yl}pentylphosphonic    acid, and (59) a compound according to (7) wherein said compound is    selected from the following compounds or a pharmacologically    acceptable salt thereof:-   3-amino-3-methyl-5-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-{1-methyl-5-[3-(4-methylphenoxy)prop-1-ynyl]pyrrol-2-yl}pentylphosphonic    acid,-   3-amino-3-methyl-5-[1-methyl-5-(4-cyclohexyloxybut-1-ynyl)pyrrol-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]pyrrol-2-yl}pentylphosphonic    acid,-   3-amino-3-methyl-5-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[1-methyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[1-methyl-5-(4-phenylbutanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[1-methyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[1-ethyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[1-ethyl-5-(4-phenylbutanoyl)pyrrol-2-yl]pentylphosphonic    acid, and-   3-amino-3-methyl-5-[1-ethyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]pentylphosphonic    acid.

Furthermore, the present invention provides the following pharmaceuticalcompositions:

-   (60) a pharmaceutical composition containing at least one    immunosuppressant selected from the group consisting of-   an agent having the action of inhibiting intracellular signal    transduction involved in cytokine expression of T-cells,-   an agent having the action of inhibiting nucleoside synthesis in    immune cells,-   an agent having the action of inhibiting the action of cytokines on    immune cells and having antirheumatic action,-   an alkylating agent causing cell death by breakdown of DNA chains or    blocking DNA synthesis,-   a metabolic antagonist inhibiting the metabolism of nucleic acids by    blocking folic acid production,-   a protein drug having the suppression action of TNF-α,-   a steroid hormone agent that binds to intracellular steroid    receptors to form a complex which binds to reaction sites on    chromosomes, resulting in the synthesis of proteins which show    immunosuppressive activity,-   a substance suppressing prostaglandin production and/or nonsteroidal    anti-inflammatory drug antagonizing the action of prostaglandin, and-   at least one compound selected from the group consisting of    compounds of the general formula (I):

[wherein,

-   -   R¹ and R² are the same or different and each represents a        hydrogen atom, a lower alkyl group, or a protecting group of the        amino group;    -   R³ represents a hydrogen atom, a lower alkyl group, or a        protecting group of the hydroxyl group;    -   R⁴ represents a lower alkyl group;    -   n represents an integer of from 1 to 6;    -   X represents a sulfur atom, an oxygen atom, or a group of        formula ═N—D (wherein D represents a hydrogen atom, an aryl        group, a lower alkylsulfonyl group, an arylsulfonyl group, or a        group selected from Substituent group (a));    -   Y represents an ethylene group, a vinylene group, an ethynylene        group, a group of formula —E—CH₂— (wherein E represents a        carbonyl group or a group of formula —CH(OH)—), a C₆–C₁₀ arylene        group, or a C₆–C₁₀ arylene group substituted with from 1 to 3        substituents selected from Substituent group (a);    -   Z represents a single bond, a C₁–C₁₀ alkylene group, a C₁–C₁₀        alkylene group substituted with from 1 to 3 substituents        selected from the group consisting of Substituent group (a) and        Substituent group (b), a C₁–C₁₀ alkylene group which has an        oxygen atom or a sulfur atom in said carbon chain or at the end        of said carbon chain, or a C₁–C₁₀ alkylene group substituted        with from 1 to 3 substituents selected from the group consisting        of Substituent group (a) and Substituent group (b) which has an        oxygen atom or a sulfur atom in said carbon chain or at the end        of said carbon chain;    -   R⁵ represents a hydrogen atom, a C₃–C₁₀ cycloalkyl group, a        C₆–C₁₀ aryl group, a 5- to 7-membered heterocyclic group        containing from 1 to 3 heteroatoms selected from the group        consisting of a sulfur atom, an oxygen atom, and a nitrogen        atom, a C₃–C₁₀ cycloalkyl group substituted with from 1 to 3        substituents selected from the group consisting of Substituent        group (a) and Substituent group (b), a C₆–C₁₀ aryl group        substituted with from 1 to 3 substituents selected from the        group consisting of Substituent group (a) and Substituent group        (b), or a 5- to 7-membered heterocyclic group containing from 1        to 3 heteroatoms selected from the group consisting of a sulfur        atom, an oxygen atom, and a nitrogen atom in which said        heterocyclic group is substituted with from 1 to 3 substituents        selected from the group consisting of Substituent group (a) and        Substituent group (b);    -   R⁶ and R⁷ are the same or different and each represents a        hydrogen atom or a group selected from Substituent group (a);    -   Substituent group (a) represents the group consisting of a        halogen atom, a lower alkyl group, a halogeno lower alkyl group,        a lower alkoxy group, a lower alkylthio group, a carboxyl group,        a lower alkoxycarbonyl group, a hydroxyl group, a lower        aliphatic acyl group, an amino group, a mono-lower alkylamino        group, a di-lower alkylamino group, a lower aliphatic acylamino        group, a cyano group, and a nitro group; and    -   Substituent group (b) represents the group consisting of a        C₆–C₁₀ cycloalkyl group, a C₆–C₁₀ aryl group, a 5- to 7-membered        heterocyclic group containing from 1 to 3 heteroatoms selected        from the group consisting of a sulfur atom, an oxygen atom, and        a nitrogen atom, a C₃–C₁₀ cycloalkyl group substituted with from        1 to 3 substituents selected from Substituent group (a), a        C₆–C₁₀ aryl group substituted with from 1 to 3 substituents        selected from Substituent group (a), and a 5- to 7-membered        heterocyclic group containing from 1 to 3heteroatoms selected        from the group consisting of a sulfur atom, an oxygen atom, and        a nitrogen atom in which said heterocyclic group is substituted        with from 1 to 3 substituents selected from Substituent group        (a);

-   provided that when R⁵ represents a hydrogen atom, then Z represents    a branched chain C₁–C₁₀ alkylene group, a C₁–C₁₀ alkylene group    substituted with from 1 to 3 substituents selected from the group    consisting of Substituent group (a) and Substituent group (b), a    C₁–C₁₀ alkylene group which has an oxygen-atom or a sulfur atom in    said carbon chain or at the end of said carbon chain, or a C₁–C₁₀    alkylene group substituted with from 1 to 3 substituents selected    from the group consisting of Substituent group (a) and Substituent    group (b) which has an oxygen atom or a sulfur atom in said carbon    chain or at the end of said carbon chain],

-   a pharmacologically acceptable salt thereof, or a pharmacologically    acceptable ester thereof.

Of these, preferred pharmaceutical compositions are:

-   (61) a pharmaceutical composition according to (60) wherein said    compound of general formula (I) has the general formula (Ia) shown    below:

(wherein, R¹, R², R³, R⁴, R⁵, R⁶, R⁷, X, Y, Z and n have the samemeanings as those indicated hereinbefore),

-   (62) a pharmaceutical composition according to (60) wherein said    compound of general formula (I) has the general formula (Ib) shown    below:

(wherein, R¹, R², R³, R⁴, R⁵, R⁶, R⁷, X, Y, Z and n have the samemeanings as those indicated hereinbefore),

-   (63) a pharmaceutical composition according to (60) wherein the    pharmacologically acceptable ester of the compound of formula (I)    has the formula (II):

(wherein, R¹, R², R⁴, R⁵, R⁶, R⁷, X, Y, Z and n have the same meaningsas those indicated hereinbefore; R¹⁰ and R¹¹ are the same or differentand each represents a hydrogen atom or a protecting group of phosphoricacid) or a pharmacologically acceptable salt thereof,

-   (64) a pharmaceutical composition according to (63) wherein the    ester of the compound of formula (II) has the formula (IIa):

(wherein, R¹, R², R⁴, R⁵, R⁶, R⁷, R¹⁰, R¹¹, X, Y, Z and n have the samemeanings as those indicated hereinbefore) or a pharmacologicallyacceptable salt thereof, and

-   (65) a pharmaceutical composition according to (63) wherein the    ester of the compound of formula (II) has the formula (IIb):

(wherein, R¹, R², R⁴, R⁵, R⁶, R⁷, R¹⁰, R¹¹, X, Y, Z and n have the samemeanings as those indicated hereinbefore) or a pharmacologicallyacceptable salt thereof.

Furthermore, the present invention provides the following pharmaceuticalcompositions:

-   (66) a pharmaceutical composition containing at least one    immunosuppressant selected from the group consisting of-   an agent having the action of inhibiting intracellular signal    transduction involved in cytokine expression of T-cells,-   an agent having the action of inhibiting nucleoside synthesis in    immune cells,-   an agent having the action of inhibiting the action of cytokines on    immune cells and having antirheumatic action,-   an alkylating agent causing cell death by breakdown of DNA chains or    blocking DNA synthesis,-   a metabolic antagonist inhibiting the metabolism of nucleic acids by    blocking folic acid production,-   a protein drug having the suppression action of TNF-α,-   a steroid hormone agent that binds to intracellular steroid    receptors to form a complex which binds to reaction sites on    chromosomes, resulting in the synthesis of proteins which show    immunosuppressive activity, and-   a substance suppressing prostaglandin production and/or nonsteroidal    anti-inflammatory drug antagonizing the action of prostaglandin, and-   at least one compound selected from the group consisting of    compounds of the general formula (III) shown below:

[wherein,

-   -   R¹ and R² are the same or different and each represents a        hydrogen atom, a lower alkyl group, or a protecting group of the        amino group;    -   R⁴ represents a lower alkyl group;    -   n represents an integer of from 1 to 6;    -   X represents a sulfur atom, an oxygen atom or a group of formula        ═N—D (wherein D represents a hydrogen atom, a C₆–C₁₀ aryl group,        a lower alkylsulfonyl group, a C₆–C₁₀ arylsulfonyl group, or a        group selected from Substituent group (a));    -   Y represents an ethylene group, a vinylene group, an ethynylene        group, a group of formula —E—CH₂— (wherein E represents a        carbonyl group or a group of formula —CH(OH)—), a C₆–C₁₀ arylene        group, or a C₆–C₁₀ arylene group substituted with from 1 to 3        substituents selected from Substituent group (a);    -   Z represents a single bond, a C₁–C₁₀ alkylene group, a C₁–C₁₀        alkylene group substituted with from 1 to 3 substituents        selected from the group consisting of Substituent group (a) and        Substituent group (b), a C₁–C₁₀ alkylene group which has an        oxygen atom or a sulfur atom in said carbon chain or at the end        of said carbon chain, or a C₁–C₁₀ alkylene group substituted        with from 1 to 3 substituents selected from the group consisting        of Substituent group (a) and Substituent group (b) which has an        oxygen atom or a sulfur atom in said carbon chain or at the end        of said carbon chain;    -   R⁵ represents a hydrogen atom, a C₃–C₁₀ cycloalkyl group, a        C₆–C₁₀ aryl group, a 5- to 7-membered heterocyclic group        containing from 1 to 3 heteroatoms selected from the group        consisting of a sulfur atom, an oxygen atom, and a nitrogen        atom, a C₃–C₁₀ cycloalkyl group substituted with from 1 to 3        substituents selected from the group consisting of Substituent        group (a) and Substituent group (b), a C₆–C₁₀ aryl group        substituted with from 1 to 3 substituents selected from the        group consisting of Substituent group (a) and Substituent group        (b), or a 5- to 7-membered heterocyclic group containing from 1        to 3 heteroatoms selected from the group consisting of a sulfur        atom, an oxygen atom, and a nitrogen atom in which said        heterocyclic group is substituted with from 1 to 3 substituents        selected from the group consisting of Substituent group (a) and        Substituent group (b);    -   R⁶ and R⁷ are the same or different and each represents a        hydrogen atom or a group selected from Substituent group (a);    -   R¹⁰ and R¹¹ are the same or different and each represents a        hydrogen atom or a protecting group of phosphoric acid;    -   Substituent group (a) represents the group consisting of a        halogen atom, a lower alkyl group, a halogeno lower alkyl group,        a lower alkoxy group, a lower alkylthio group, a carboxyl group,        a lower alkoxycarbonyl group, a hydroxyl group, a lower        aliphatic acyl group, an amino group, a mono-lower alkylamino        group, a di-lower alkylamino group, a lower aliphatic acylamino        group, a cyano group, and a nitro group; and    -   Substituent group (b) represents the group consisting of a        C₃–C₁₀ cycloalkyl group, a C₆–C₁₀ aryl group, a 5- to 7-membered        heterocyclic group containing from 1 to 3 heteroatoms selected        from the group consisting of a sulfur atom, an oxygen atom, and        a nitrogen atom, a C₃–C₁₀ cycloalkyl group substituted with from        1 to 3 substituents selected from Substituent group (a), a        C₆–C₁₀ aryl group substituted with from 1 to 3 substituents        selected from Substituent group (a), and a 5- to 7-membered        heterocyclic group containing from 1 to 3 heteroatoms selected        from the group consisting of a sulfur atom, an oxygen atom, and        a nitrogen atom in which said heterocyclic group is substituted        with from 1 to 3 substituents selected from Substituent group        (a);

-   provided that when R⁵ represents a hydrogen atom, then Z represents    a branched chain C₁–C₁₀ alkylene group, a C₁–C₁₀ alkylene group    substituted with from 1 to 3 substituents selected from the group    consisting of Substituent group (a) and Substituent group (b), a    C₁–C₁₀ alkylene group which has an oxygen atom or a sulfur atom in    said carbon chain or at the end of said carbon chain, or a C₁–C₁₀    alkylene group substituted with from 1 to 3 substituents selected    from the group consisting of Substituent group (a) and Substituent    group (b) which has an oxygen atom or a sulfur atom in said carbon    chain or at the end of said carbon chain],

-   a pharmacologically acceptable salt thereof, or a

-   pharmacologically acceptable ester thereof.

Of these, preferred pharmaceutical compositions are:

-   (67) a pharmaceutical composition according to (66) Wherein the    compound of formula (III) has the formula (IIIa):

(wherein, R¹, R², R⁴, R⁵, R⁶, R⁷, R¹⁰, R¹¹, X, Y, Z and n have the samemeanings as those indicated hereinbefore), and

-   (68) a pharmaceutical composition according to (66) wherein the    compound of formula (III) has the formula (IIIb)

(wherein, R¹, R², R⁴, R⁵, R⁶, R⁷, R¹⁰, R¹¹, X, Y, Z and n have the samemeanings as those indicated hereinbefore).

Of these, more preferred pharmaceutical compositions are:

-   (69) a pharmaceutical composition according to any one of (60)    to (68) containing a compound wherein R¹ and R² are the same or    different and each represents a hydrogen atom, a lower aliphatic    acyl group, a lower alkoxycarbonyl group, an aralkyloxycarbonyl    group, or an aralkyloxycarbonyl group substituted with from 1 to 3    substituents selected from Substituent group (a), or a    pharmacologically acceptable salt thereof,-   (70) a pharmaceutical composition according to any one of (60)    to (68) containing a compound wherein R¹ and R² are the same or    different and each represents a hydrogen atom, a lower aliphatic    acyl group, or a lower alkoxycarbonyl group, or a pharmacologically    acceptable salt thereof,-   (71) a pharmaceutical composition according to any one of (60)    to (68) containing a compound wherein R¹ and R² are the same or    different and each represents a hydrogen atom, a C₁–C₄ aliphatic    acyl group, or a C₁–C₄ alkoxycarbonyl group, or a. pharmacologically    acceptable salt thereof,-   (72) a pharmaceutical composition according to any one of (60)    to (68) containing a compound wherein R¹ and R² are the same or    different and each represents a hydrogen atom, a C₁–C₂ aliphatic    acyl group, or a C₁–C₂ alkoxycarbonyl group, or a pharmacologically    acceptable salt thereof,-   (73) a pharmaceutical composition according to any one of (60)    to (68) containing a compound wherein R¹ and R² are the same or    different and each represents a hydrogen atom, an acetyl group, or a    methoxycarbonyl group, or a pharmacologically acceptable salt    thereof,-   (74) a pharmaceutical composition according to any one of (60)    to (68) containing a compound wherein each of R¹ and R² represents a    hydrogen atom, or a pharmacologically acceptable salt thereof,-   (75) a pharmaceutical composition according to any one of (60)    to (62) and (69) to (74) containing a compound wherein R³ represents    a hydrogen atom, a lower alkyl group, a lower aliphatic acyl group,    an aromatic acyl group, an aromatic acyl group substituted with from    1 to 3 substituents selected from Substituent group (a), or a silyl    group, or a pharmacologically acceptable salt thereof,-   (76) a pharmaceutical composition according to any one of (60)    to (62) and (69) to (74) containing a compound wherein R³ represents    a hydrogen atom or a lower alkyl group, or a pharmacologically    acceptable salt thereof,-   (77) a pharmaceutical composition according to any one of (60)    to (62) and (69) to (74) containing a compound wherein R³ represents    a hydrogen atom or a C₁–C₄ alkyl group, or a pharmacologically    acceptable salt thereof,-   (78) a pharmaceutical composition according to any one of (60)    to (62) and (69) to (74) containing a compound wherein R³ represents    a hydrogen atom, a methyl group, or an ethyl group, or a    pharmacologically acceptable salt thereof,-   (79) a pharmaceutical composition according to any one of (60)    to (62) and (69) to (74) containing a compound wherein R³ represents    a hydrogen atom, or a pharmacologically acceptable salt thereof,-   (80) a pharmaceutical composition according to any one of (60)    to (79) containing a compound wherein R⁴ represents a C₁–C₄ alkyl    group, or a pharmacologically acceptable salt thereof.-   (81) a pharmaceutical composition according to any one of (60)    to (79) containing a compound wherein R⁴ represents a C₁–C₂ alkyl    group, or a pharmacologically acceptable salt thereof,-   (82) a pharmaceutical composition according to any one of (60)    to (79) containing a compound wherein R⁴ represents a methyl group,    or a pharmacologically acceptable salt thereof,-   (83) a pharmaceutical composition according to any one of (60)    to (82) containing a compound wherein n represents an integer 2 or    3, or a pharmacologically acceptable salt thereof,-   (84) a pharmaceutical composition according to any one of (60)    to (82) containing a compound wherein n represents an integer 2, or    a pharmacologically acceptable salt thereof,-   (85) a pharmaceutical composition according to any one of (60)    to (84) containing a compound wherein X represents a sulfur atom, or    a pharmacologically acceptable salt thereof,-   (86) a pharmaceutical composition according to any one of (60)    to (84) containing a compound wherein X represents an oxygen atom,    or a pharmacologically acceptable salt thereof,-   (87) a pharmaceutical composition according to any one of (60)    to (84) containing a compound wherein X represents a group of    formula ═N—D (wherein D represents a hydrogen atom, a C₁–C₄ alkyl    group, or a phenyl group), or a pharmacologically acceptable salt    thereof,-   (88) a pharmaceutical composition according to any one of (60)    to (84) containing a compound wherein X represents a group of    formula ═N—CH₃, or a pharmacologically acceptable salt thereof,-   (89) a pharmaceutical composition according to any one of (60)    to (88) containing a compound wherein Y represents an ethylene    group, an ethynylene group, a group of formula —CO—CH₂—, a group of    formula —CH(OH)—CH₂—, a phenylene group, or a phenylene group    substituted with from 1 to 3 substituents selected from the group    consisting of a halogen atom and a lower alkyl group, or a    pharmacologically acceptable salt thereof,-   (90) a pharmaceutical composition according to any one of (60)    to (88) containing a compound wherein Y represents an ethylene    group, an ethynylene group, a group of formula —CO—CH₂—, or a    phenylene group, or a pharmacologically acceptable salt thereof,-   (91) a pharmaceutical composition according to any one of (60)    to (90) containing a compound wherein Z represents a C₁–C₁₀ alkylene    group or a C₁–C₁₀ alkylene group substituted with from 1 to 3    substituents selected from the group consisting of Substituent    group (a) and Substituent group (b), or a pharmacologically    acceptable salt thereof,-   (92) a pharmaceutical composition according to any one of (60)    to (90) containing a compound wherein Z represents a C₁–C₆ alkylene    group or a C₁–C₆ alkylene group substituted with from 1 to 3    hydroxyl groups, or a pharmacologically acceptable salt thereof,-   (93) a pharmaceutical composition according to any one of (60)    to (90) containing a compound wherein Z represents a C₁–C₅ alkylene    group or a C₁–C₅ alkylene group substituted with from 1 to 3    hydroxyl groups, or a pharmacologically acceptable salt thereof,-   (94) a pharmaceutical composition according to any one of (60)    to (90) containing a compound wherein Z represents an ethylene    group, a trimethylene group, a tetramethylene group, or an ethylene,    trimethylene, or tetramethylene group substituted with one hydroxyl    group, or a pharmacologically acceptable salt thereof,-   (95) a pharmaceutical composition according to any one of (60)    to (90) containing a compound wherein Z represents an ethylene    group, a trimethylene group, or a tetramethylene group, or a    pharmacologically acceptable salt thereof,-   (96) a pharmaceutical composition according to any one of (60)    to (90) containing a compound wherein Z represents an ethylene group    or a trimethylene group, or a pharmacologically acceptable salt    thereof,-   (97) a pharmaceutical composition according to any one of (60)    to (90) containing a compound wherein Z represents a C₁–C₁₀ alkylene    group which has an oxygen atom or a sulfur atom in said carbon chain    or at the end of said carbon chain or a C₁–C₁₀ alkylene group    substituted with one substituent which has an oxygen atom or a    sulfur atom in said carbon chain or at the end of said carbon chain    (said substituent is selected from the group consisting of lower    alkyl groups and hydroxyl groups), or a pharmacologically acceptable    salt thereof,-   (98) a pharmaceutical composition according to any one of (60)    to (90) containing a compound wherein Z represents a C₁–C₁₀ alkylene    group which has an oxygen atom or a sulfur atom in said carbon chain    or at the end of said carbon chain, or a pharmacologically    acceptable salt thereof,-   (99) a pharmaceutical composition according to any one of (60)    to (90) containing a compound wherein Z represents a C₁–C₁₀ alkylene    group which has an oxygen atom in said carbon chain or at the end of    said carbon chain, or a pharmacologically acceptable salt thereof,-   (100) a pharmaceutical composition according to any one of (60)    to (90) containing a compound wherein Z represents a C₁–C₆ alkylene    group which has an oxygen atom in said carbon chain or at the end of    said carbon chain, or a pharmacologically acceptable salt thereof,-   (101) a pharmaceutical composition according to any one of (60)    to (90) containing a compound wherein Z represents a group of    formula —O—CH₂—, —O—(CH₂)₂—, —O—(CH₂)₃—, —CH₂—O—, —(CH₂)₂—O—, or    —(CH₂)₃—O—, or a pharmacologically acceptable salt thereof,-   (102) a pharmaceutical composition according to any one of (60)    to (90) containing a compound wherein Z represents a group of    formula —CH₂—O— or —(CH₂)₂—O—, or a pharmacologically acceptable    salt thereof,-   (103) a pharmaceutical composition according to any one of (60)    to (102) containing a compound wherein R⁵ represents a hydrogen    atom, or a pharmacologically acceptable salt thereof,-   (104) a pharmaceutical composition according to any one of (60)    to (102) containing a compound wherein R⁵ represents a C₃–C₁₀    cycloalkyl group, a C₆–C₁₀ aryl group, or a C₃–C₁₀ cycloalkyl or    C₆–C₁₀ aryl group substituted with from 1 to 3 substituents selected    from the group consisting of a halogen atom, a lower alkyl group, a    halogeno lower alkyl group, a lower alkoxy group, and a lower    alkylthio group, or a pharmacologically acceptable salt thereof,-   (105) a pharmaceutical composition according to any one of (60)    to (102) containing a compound wherein R⁵ represents a C₃–C₁₀    cycloalkyl group, a C₆–C₁₀ aryl group, or a C₃–C₁₀ cycloalkyl or    C₆–C₁₀ aryl group substituted with from 1 to 3 substituents selected    from the group consisting of a halogen atom, a lower alkyl group, a    halogeno lower alkyl group, and a lower alkoxy group, or a    pharmacologically acceptable salt thereof,-   (106) a pharmaceutical composition according to any one of (60)    to (102) containing a compound wherein R⁵ represents a C₅–C₆    cycloalkyl group, a phenyl group, or a naphthyl group, or a    pharmacologically acceptable salt thereof,-   (107) a pharmaceutical composition according to any one of (60)    to (102) containing a compound wherein R⁵ represents a cyclohexyl    group or a phenyl group, or a pharmacologically acceptable salt    thereof,-   (108) a pharmaceutical composition according to any one of (60)    to (107) containing a compound wherein R⁶ and R⁷ are the same or    different and each represents a hydrogen atom, a halogen atom, a    lower alkyl group, a halogeno lower alkyl group, a lower alkoxy    group, or a lower alkylthio group, or a pharmacologically acceptable    salt thereof,-   (109) a pharmaceutical composition according to any one of (60)    to (107) containing a compound wherein each of R⁶ and R⁷ represents    a hydrogen atom, or a pharmacologically acceptable salt thereof,-   (110) a pharmaceutical composition according to any one of (63)    to (74) and (80) to (109) containing a compound wherein R¹⁰ and R¹¹    are the same or different and each represents a hydrogen atom or a    lower alkyl group, or a pharmacologically acceptable salt thereof,-   (111) a pharmaceutical composition according to any one of (63)    to (74) and (80) to (109) containing a compound wherein R¹⁰ and R¹¹    are the same or different and each represents a hydrogen atom or a    C₁–C₄ alkyl group, or a pharmacologically acceptable salt thereof,-   (112) a pharmaceutical composition according to any one of (63)    to (74) and (80) to (109) containing a compound wherein R¹⁰ and R¹¹    are the same or different and each represents a hydrogen atom, a    methyl group or an ethyl group, or a pharmacologically acceptable    salt thereof, and-   (113) a pharmaceutical composition according to any one of (63)    to (74) and (80) to (109) containing a compound wherein each of R¹⁰    and R¹¹ represents a hydrogen atom, or a pharmacologically    acceptable salt thereof.

Of these, particularly preferred pharmaceutical compositions are:

-   (114) a pharmaceutical composition according to (60), wherein the    compound of general formula (I), or pharmacologically acceptable    salt thereof, or pharmacologically acceptable ester thereof is    selected from the group consisting of the compounds described below,    pharmacologically acceptable salts thereof, and pharmacologically    acceptable esters thereof:-   2-amino-2-methyl-4-[5-(4-cyclohexylbutyl)thiophen-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[5-(5-cyclohexylpentyl)thiophen-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[5-(5-phenylpentyl)thiophen-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[5-(4-cyclohexyloxybutyl)thiophen-2-yl]butan-1-ol,-   2-amino-2-methyl-4-{5-[4-(4-fluorophenoxy)butyl]thiophen-2-yl)butan-1-ol,-   2-amino-2-methyl-4-{5-[4-(4-methoxyphenoxy)butyl]thiophen-2-yl}butan-1-ol-   2-amino-2-methyl-4-[5-(4-benzyloxybutyl)thiophen-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[5-(4-cyclohexylbut-1-ynyl)thiophen-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[5-(4-phenylbut-1-ynyl)thiophen-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[5-(4-cyclohexylpent-1-ynyl)thiophen-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)thiophen-2-yl]butan-1-ol,-   2-amino-2-methyl-4-{5-[5-(4-fluorophenyl)pent-1-ynyl]thiophen-2-yl}butan-1-ol,-   2-amino-2-methyl-4-{5-[5-(4-methoxyphenyl)pent-1-ynyl]thiophen-2-yl}butan-1-ol,-   2-amino-2-methyl-4-{5-[3-(4-methylphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   2-amino-2-methyl-4-{5-[3-(4-ethylphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   2-amino-2-methyl-4-{5-[3-(4-methylthiophenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)thiophen-2-yl]butan-1-ol,-   2-amino-2-methyl-4-{5-[4-(4-fluorophenoxy)but-1-ynyl]thiophen-2-yl}butan-1-ol,-   2-amino-2-methyl-4-{5-[4-(4-methylphenoxy)but-1-ynyl]thiophen-2-yl}butan-1-ol,-   2-amino-2-methyl-4-[5-(3-cyclohexylmethoxyprop-1-ynyl)thiophen-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[5-(4-benzyloxybut-1-ynyl)thiophen-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[5-(4-cyclohexylbutanoyl)thiophen-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[5-(4-phenylbutanoyl)thiophen-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[5-(5-phenylpentanoyl)thiophen-2-yl]butan-1-ol,-   2-amino-2-methyl-4-{5-[5-(4-fluorophenyl)pentanoyl]thiophen-2-yl}butan-1-ol,-   2-amino-2-ethyl-4-[5-(5-cyclohexylpentyl)thiophen-2-yl]butan-1-ol,-   2-amino-2-ethyl-4-[5-(5-cyclohexylpent-1-ynyl)thiophen-2-yl]butan-1-ol,-   2-amino-2-ethyl-4-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]butan-1-ol,-   2-amino-2-methyl-4-{5-[3-(4-chlorophenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   2-amino-2-methyl-4-{5-[3-(3-methylphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   2-amino-2-methyl-4-{5-[3-(3-methoxyphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   2-amino-2-methyl-4-{5-[3-(3,4-dimethoxyphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   2-amino-2-methyl-4-{5-[3-(3,5-dimethoxyphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   2-amino-2-methyl-4-{5-[3-(3-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,    and-   2-amino-2-methyl-4-{5-[3-(4-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   (115) a pharmaceutical composition according to (60), wherein the    compound of general formula (I), or pharmacologically acceptable    salt thereof, or pharmacologically acceptable ester thereof is    selected from the group consisting of the compounds described below,    pharmacologically acceptable salts thereof, and pharmacologically    acceptable esters thereof:-   2-amino-2-methyl-4-[5-(5-phenylpentyl)furan-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)furan-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)furan-2-yl]butan-1-ol,    and-   2-amino-2-methyl-4-(5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]furan-2-yl)butan-1-ol,-   (116) a pharmaceutical composition according to (60), wherein the    compound of general formula (I), or pharmacologically acceptable    salt thereof, or pharmacologically acceptable ester thereof is    selected from the group consisting of the compounds described below,    pharmacologically acceptable salts thereof, and pharmacologically    acceptable esters thereof:-   2-amino-2-methyl-4-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]butan-1-ol,-   2-amino-2-methyl-4-(1-methyl-5-[3-(4-methylphenoxy)prop-1-ynyl]pyrrol-2-yl}butan-1-ol,-   2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexyloxybut-1-ynyl)pyrrol-2-yl]butan-1-ol,-   2-amino-2-methyl-4-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]pyrrol-2-yl}butan-1-ol,-   2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[1-methyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[1-methyl-5-(4-phenylbutanoyl)pyrrol-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]butan-1-ol,-   2-amino-2-methyl-4-{1-methyl-5-[4-(4-methylphenyl)butanoyl)pyrrol-2-yl}butan-1-ol,-   2-amino-2-methyl-4-[1-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol,-   2-amino-2-methyl-4-[1-ethyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]butan-1-ol,-   2-amino-2-methyl-4-(1-ethyl-5-(4-phenylbutanoyl)pyrrol-2-yl]butan-1-ol,    and-   2-amino-2-methyl-4-[1-ethyl-5-(4-cyclohexylbutanoyl)pyrrol-2-y1]butan-1-ol,-   2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol,-   2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol-   2-amino-2-methyl-4-{1-methyl-5-[4-(3-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol,-   2-amino-2-methyl-4-{1-methyl-5-[4-(4-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol,-   2-amino-2-methyl-4-{1-methyl-5-[4-(4-methoxyphenyl)butanoyl]pyrrol-2-yl}butan-1-ol,-   2-amino-2-methyl-4-(1-methyl-5-[4-(3-methylphenyl)butyl]pyrrol-2-yl)butan-1-ol,-   2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol,-   2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butyl]pyrrol-2-yl)butan-1-ol-   2-amino-2-methyl-4-{1-methyl-5-[4-(3-trifluoromethylphenyl)butyl)pyrrol-2-yl]butan-1-ol.-   (117) a pharmaceutical composition according to (63), wherein the    compound of general formula (II), or pharmacologically acceptable    gait thereof, or pharmacologically acceptable eater thereof in    selected from the group consisting of the compounds described below,    pharmacologically acceptable salts thereof, and pharmacologically    acceptable esters thereof:-   mono 2-amino-2-methyl-4-[5-(4-cyclohexylbutyl)thiophen-2-yl]-1-butyl    phosphate,-   mono 2-amino-2-methyl-4-[5-(5-cyclohexylpentyl)    thiophen-2-yl]-1-butyl phosphate,-   mono 2-amino-2-methyl-4-[5-(5-phenylpentyl)thiophen-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[5-(4-cyclohexyloxybutyl)thiophen-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{5-[4-(4-fluorophenoxy)butyl]thiophen-2-yl}-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-(5-[4-(4-methoxyphenoxy)butyl]thiophen-2-yl}-1-butyl    phosphate,-   mono 2-amino-2-methyl-4-[5-(4-benzyloxybutyl)thiophen-2-yl)-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[5-(4-cyclohexylbut-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[5-(4-phenylbut-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{5-[5-(4-fluorophenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{5-[5-(4-methoxyphenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{5-[3-(4-methylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{5-[3-(4-ethylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{5-[3-(4-methylthiophenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   mono-2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{5-[4-(4-fluorophenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{5-[4-(4-methylphenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[5-(3-cyclohexylmethoxy)prop-1-ynyl]thiophen-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[5-(4-benzyloxybut-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[5-(4-cyclohexylbutanoyl)thiophen-2-yl]-1-butyl    phosphate,-   mono 2-amino-2-methyl-4-[5-(4-phenylbutanoyl)thiophen-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]-1-butyl    phosphate,-   mono 2-amino-2-methyl-4-[5-(5-phenylpentanoyl)thiophen-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{5-[5-(4-fluorophenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   mono 2-amino-2-ethyl-4-[5-(5-cyclohexylpentyl)thiophen-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-ethyl-4-[5-(5-cyclohexylpent-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-ethyl-4-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{5-[3-(4-chlorophenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{5-[3-(3-methylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{5-[3-(3-methoxyphenoxyl)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{5-[3-(3,4-dimethoxyphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{5-[3-(3,5-dimethoxyphenoxyl)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{5-[3-(3-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate, and-   mono    2-amino-2-methyl-4-{5-[3-(4-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   (118) a pharmaceutical composition according to (63), wherein the    compound of general formula (II), or pharmacologically acceptable    salt thereof, or pharmacologically acceptable ester thereof is    selected from the group consisting of the compounds described below,    pharmacologically acceptable salts thereof, and pharmacologically    acceptable esters thereof:-   mono 2-amino-2-methyl-4-[5-(5-phenylpentyl)furan-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]-1-butyl    phosphate,-   mono 2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)furan-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)furan-2-yl]-1-butyl    phosphate, and-   mono    2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]furan-2-yl}-1-butyl    phosphate,-   (119) a pharmaceutical composition according to (63), wherein the    compound of general formula (II), or pharmacologically acceptable    salt thereof, or pharmacologically acceptable ester thereof is    selected from the group consisting of the compounds described below,    pharmacologically acceptable salts thereof, and pharmacologically    acceptable esters thereof:-   mono    2-amino-2-methyl-4-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{1-methyl-5-[3-(4-methylphenoxy)prop-1-ynyl]pyrrol-2-yl}-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexyloxybut-1-ynyl)pyrrol-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]pyrrol-2-yl}-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[1-methyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[1-methyl-5-(4-phenylbutanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[1-methyl-5-{4-(4-methylphenyl)butanoyl]pyrrol-2-yl}-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[1-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[1-ethyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-[1-ethyl-5-(4-phenylbutanoyl)pyrrol-2-yl]-1-butyl    phosphate, and-   mono    2-amino-2-methyl-4-[1-ethyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butanoyl]pyrrol-2-yl}-1-butyl    phosphate,-   mono    2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butanoyl]pyrrol-2-yl}-1-butyl    phosphate.-   (120) a pharmaceutical composition according to (66), wherein the    compound of general formula (III), or pharmacologically acceptable    salt thereof, or pharmacologically acceptable ester thereof is    selected from the group consisting of the compounds described below,    pharmacologically acceptable salts thereof, and pharmacologically    acceptable esters thereof:-   3-amino-3-methyl-5-[5-(4-cyclohexylbutyl)thiophen-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[5-(5-cyclohexylpentyl)thiophen-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[5-(5-phenylpentyl)thiophen-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[5-(4-cyclohexyloxybutyl)thiophen-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-{5-[4-(4-fluorophenoxy)butyl]thiophen-2-yl}pentylphosphonic    acid,-   3-amino-3-methyl-5-{5-[4-(4-methoxyphenoxy)butyl]thiophen-2-yl}pentylphosphonic    acid,-   3-amino-3-methyl-5-[5-(4-benzyloxybutyl)thiophen-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[5-(4-cyclohexylbut-1-ynyl)thiophen-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[5-(4-phenylbut-1-ynyl)thiophen-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[5-(5-cyclohexylpent-1-ynyl)thiophen-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[5-(5-phenylpent-1-ynyl)thiophen-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-{5-[5-(4-fluorophenyl)pent-1-ynyl]thiophen-2-yl}pentylphosphonic    acid,-   3-amino-3-methyl-5-{5-[5-(4-methoxyphenyl)pent-1-ynyl]thiophen-2-yl}pentylphosphonic    acid,-   3-amino-3-methyl-5-{5-[3-(4-methylphenoxy)prop-1-ynyl)thiophen-2-yl}pentylphosphonic    acid,-   3-amino-3-methyl-5-{5-[3-(4-ethylphenoxy)prop-1-ynyl]thiophen-2-yl}pentylphosphonic    acid,-   3-amino-3-methyl-5-{5-[3-(4-methylthiophenoxy)prop-1-ynyl]thiophen-2-yl}pentylphosphonic    acid,-   3-amino-3-methyl-5-[5-(4-cyclohexyloxybut-1-ynyl)thiophen-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-{5-[4-(4-fluorophenoxy)but-1-ynyl]thiophen-2-yl}pentylphosphonic    acid,-   3-amino-3-methyl-5-{5-[4-(4-methylphenoxy)but-1-ynyl]thiophen-2-yl}pentylphosphonic    acid,-   3-amino-3-methyl-5-[5-(3-cyclohexylmethoxy)prop-1-ynyl]thiophen-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[5-(4-benzyloxybut-1-ynyl)thiophen-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[5-(4-cyclohexylbutanoyl)thiophen-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[5-(4-phenylbutanoyl)thiophen-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[5-(5-phenylpentanoyl)thiophen-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-{5-[5-(4-fluorophenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   3-amino-3-ethyl-5-[5-(5-cyclohexylpentyl)thiophen-2-yl]pentylphosphonic    acid,-   3-amino-3-ethyl-5-[5-(5-cyclohexylpent-1-ynyl)thiophen-2-yl]pentylphosphonic    acid,-   3-amino-3-ethyl-5-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-{5-[3-(4-chlorophenoxy)prop-1-ynyl]thiophen-2-yl}pentylphosphonic    acid,-   3-amino-3-methyl-5-{5-[3-(3-methylphenoxy)prop-1-ynyl]thiophen-2-yl}pentylphosphonic    acid,-   3-amino-3-methyl-5-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]thiophen-2-yl}pentylphosphonic    acid,-   3-amino-3-methyl-5-{5-[3-(3-methoxyphenoxyl)prop-1-ynyl]thiophen-2-yl}pentylphosphonic    acid,-   3-amino-3-methyl-5-{5-[3-(3,4-dimethoxyphenoxy)prop-1-ynyl]thiophen-2-yl}pentylphosphonic    acid,-   3-amino-3-methyl-5-{5-[3-(3,5-dimethoxyphenoxyl)prop-1-ynyl]thiophen-2-yl}pentylphosphonic    acid,-   3-amino-3-methyl-5-{5-[3-(3-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}pentylphosphonic    acid, and-   3-amino-3-methyl-5-{5-[3-(4-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}pentylphosphonic    acid,-   (121) a pharmaceutical composition according to (66), wherein the    compound of general formula (III), or pharmacologically acceptable    salt thereof, or pharmacologically acceptable ester thereof is    selected from the group consisting of the compounds described below,    pharmacologically acceptable salts thereof, and pharmacologically    acceptable esters thereof:-   3-amino-3-methyl-5-[5-(5-phenylpentyl)furan-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[5-(5-phenylpent-1-ynyl)furan-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[5-(5-cyclohexylpentanoyl)furan-2-yl]pentylphosphonic    acid, and-   3-amino-3-methyl-5-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]furan-2-yl}pentylphosphonic    acid,-   (122) a pharmaceutical composition according to (66), wherein the    compound of general formula (III), or pharmacologically acceptable    salt thereof, or pharmacologically acceptable ester thereof is    selected from the group consisting of the compounds described below,    pharmacologically acceptable salts thereof, and pharmacologically    acceptable esters thereof:-   3-amino-3-methyl-5-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-{1-methyl-5-[3-(4-methylphenoxy)prop-1-ynyl]pyrrol-2-yl}pentylphosphonic    acid,-   3-amino-3-methyl-5-[1-methyl-5-(4-cyclohexyloxybut-1-ynyl)pyrrol-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]pyrrol-2-yl}pentylphosphonic    acid,-   3-amino-3-methyl-5-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[1-methyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[1-methyl-5-(4-phenylbutanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[1-methyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[1-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[1-ethyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   3-amino-3-methyl-5-[1-ethyl-5-(4-phenylbutanoyl)pyrrol-2-yl]pentylphosphonic    acid, and-   3-amino-3-methyl-5-[1-ethyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   (123) a pharmaceutical composition according to any one of (60)    to (122) wherein said composition contains at least one    immunosuppressant selected from the group consisting of agents    having the action of inhibiting intracellular signal transduction    involved in cytokine expression of T-cells (said agents are    cyclosporin A, tacrolimus, rapamycin, gusperimus, everolimus,    tresperimus, anisperimus, SDZ-281-240, ABT-281, tigderimus,    A-119435, or    17-ethyl-1,14-dihydroxy-12-[2-[4-(2-phenylhydrazinocarbonyloxy)-3-methoxycyclohexyl]-1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0^(4,9)]octacos-18-ene-2,3,10,16-tetrone),-   agents having the action of inhibiting nucleoside synthesis in    immune cells (said agents are mizoribine, azathioprine,    mycophenolate Mofetil, leflunomide, merimempodib, HMR-1279, TSK-204,    or SP-100030),-   agents having the action of inhibiting the action of cytokines on    immune cells and having antirheumatic action (said agents are T-614,    actarit, salazosulfapyridine, or CDC-801),-   alkylating agents causing cell death by breakdown of DNA chains or    blocking DNA synthesis (said alkylating agent is cyclophosphamide),-   metabolic antagonists inhibiting the metabolism of nucleic acids by    blocking folic acid production (said metabolic antagonist is    methotrexate),-   protein drugs having the suppression action of TNF-α (said protein    drugs are remicade, enbrel, daclizumab, basiliximab, alemtuzumab,    omalizumab, BMS-188667, CDP-571, inolimomab, ATM-027, or BTI-322),-   steroid hormone agents that bind to intracellular steroid receptors    to form a complex which binds to reaction sites on chromosomes,    resulting in the synthesis of proteins which show immunosuppressive    activity (said steroid hormone agent is prednisolone), and-   substances suppressing prostaglandin production and/or nonsteroidal    anti-inflammatory drugs antagonizing the action of prostaglandin    (said nonsteroidal anti-inflammatory drugs are loxoprofen sodium,    diclofenac sodium, meloxicam, celecoxib, or rofecoxib), and-   (124) a pharmaceutical composition according to any one of (60)    to (122) wherein said composition contains at least one    immunosuppressant selected from the group consisting of cyclosporin    A, tacrolimus, rapamycin, leflunomide, methotrexate, remicade, and    enbrel.

Another object of the present invention is to provide the followingpharmaceutical compositions and methods:

-   (125) a pharmaceutical composition comprising as an active    ingredient a compound, a pharmacologically acceptable salt thereof    or a pharmacologically acceptable ester thereof according to any one    of (1) to (59),-   (126) a pharmaceutical composition according to (125) for the    prevention or treatment of autoimmune diseases,-   (127) a pharmaceutical composition according to (126) wherein said    autoimmune disease is rheumatoid arthritis,-   a pharmaceutical composition according to (126) wherein said    autoimmune disease is Crohn's disease orulcerative colitis,-   a pharmaceutical composition according to (126) wherein said    autoimmune disease is multiple sclerosis,-   a pharmaceutical composition according to (126) wherein said    autoimmune disease is psoriasis,-   a pharmaceutical composition according to (126) wherein said    autoimmune disease is atopic dermatitis,-   a pharmaceutical composition according to (126) wherein said    autoimmune disease is insulin dependent diabetes mellitus,-   a pharmaceutical composition according to (126) wherein said    autoimmune disease is glomerular nephritis,-   (128) a pharmaceutical composition according to (125) for    suppression of rejection caused by transplantation of various organs    or skin,-   (129) a method for the prevention or treatment of autoimmune    diseases in a mammal which comprises administering to said mammal an    effective amount of a pharmaceutical composition according to any    one of (60) to (125),-   (130) a method for the prevention or treatment of rheumatoid    arthritis in a mammal which comprises administering to said mammal    an effective amount of a pharmaceutical composition according to any    one of (60) to (125), and-   a method for the prevention or treatment of psoriasis in a mammal    which comprises administering to said mammal an effective amount of    a pharmaceutical composition according to any one of (60) to (125),-   a method for the prevention or treatment of Crohn's disease or    ulcerative colitis in a mammal which comprises administering to said    mammal an effective amount of a pharmaceutical composition according    to any one of (60) to (125),-   a method for the prevention or treatment of multiple sclerosis in a    mammal which comprises administering to said mammal an effective    amount of a pharmaceutical composition according to any one of (60)    to (125),-   a method for the prevention or treatment of atopic dermatitis in a    mammal which comprises administering to said mammal an effective    amount of a pharmaceutical composition according to any one of    claims 60 to 125.-   a method for the prevention or treatment of insulin dependent    diabetes mellitus in a mammal which comprises administering to said    mammal an effective amount of a pharmaceutical composition according    to any one of claims 60 to 125.-   a method for the prevention or treatment of glomerular nephritis in    a mammal which comprises administering to said mammal an effective    amount of a pharmaceutical composition according to any one of    claims 60 to 125.-   (131) a method for the prevention or treatment of rejection caused    by transplantation of various organs or skin in a mammal which    comprises administering to said mammal an effective amount of a    pharmaceutical composition according to any one of (60) to (125).

In the formulae (I), (II) and (III), the aryl moiety of the “C₆–C₁₀ arylgroup”, the “C₆–C₁₀ aryl group which is substituted with from 1 to 3substituents selected from Substituent group (a)”, or the “C₆–C₁₀ arylgroup which is substituted with from 1 to 3 substituents selected fromthe group consisting of Substituent group (a) and Substituent group (b)”in the definition of D, R⁵ or Substituent group (b) can be, for example,a group such as a phenyl, indenyl, or naphthyl group, and is preferablya phenylene or naphthylene group, and most preferably a phenylene group.

The arylene moiety of the “C₆–C₁₀ rylene group”, the “C₆–C₁₀ arylenegroup which is substituted with from 1 to 3 substituents selected fromSubstituent group (a)”, or the “C₆–C₁₀ arylene group which issubstituted with from 1 to 3 substituents selected from the groupconsisting of Substituent group (a) and Substituent group (b)” in thedefinition of Y or E can be, for example, a group such as a phenylene,indenylene, or naphthylene group, and is preferably a phenylene ornaphthylene group, and most preferably a phenylene group.

The C₁–C₁₀ alkylene moiety of the “C₁–C₁₀ alkylene group” or the“C₁–C₁₀alkylene group which is substituted with from 1 to 3 substituentsselected from the group consisting of Substituent group (a) andSubstituent group (b)”, in the definition of Z includes straight orbranched chain alkylene groups having from 1 to 10 carbon atoms, and canbe, for example, a group such as a methylene, methylmethylene, ethylene,propylene, trimethylene, 1-methylethylene, tetramethylene,1-methyltrimethylene, 2-methyltrimethylene, 3-methyltrimethylene,1-methylpropylene, 1,1-dimethylethylene, pentamethylene,1-methyltetramethylene, 2-methyltetramethylene, 3-methyltetramethylene,4-methyltetramethylene, 1,1-dimethyltrimethylene,2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene, hexamethylene,1-methylpentamethylene, 2-methylpentamethylene, 3-methylpentamethylene,4-methylpentamethylene, 5-methylpentamethylene,1,1-dimethyltetramethylene, 2,2-dimethyltetramethylene,3,3-dimethyltetramethylene, 4,4-dimethyltetramethylene, heptamethylene,1-methylhexamethylene, 2-methylhexamethylene, 5-methylhexamethylene,3-ethylpentamethylene, octamethylene, 2-methylheptamethylene,5-methylheptamethylene, 2-ethylhexamethylene,2-ethyl-3-methylpentamethylene, 3-ethyl-2-methylpentamethylene,nonamethylene, 2-methyloctamethylene, 7-methyloctamethylene,4-ethylheptamethylene, 3-ethyl-2-methylhexamethylene,2-ethyl-1-methylhexamethylene or decamethylene group, and is preferablya C₁–C₆ alkylene group, more preferably a C₁–C₅ alkylene group, stillmore preferably an ethylene, trimethylene, or tetramethylene group, andmost preferably an ethylene or trimethylene group.

The “C₁–C₁₀ alkylene moiety which contains an oxygen atom or a sulfuratom in the carbon chain or at the end of the carbon chain” of the“C₁–C₁₀ alkylene group which has an oxygen atom or a sulfur atom in saidcarbon chain or at the end of said carbon chain” or the “C₁–C₁₀ alkylenegroup substituted with from 1 to 3 substituents selected from the groupconsisting of Substituent group (a) and Substituent group (b) which hasan oxygen atom or a sulfur atom in said carbon chain or at the end ofsaid carbon chain” in the definition of Z represents a “C₁–C₁₀ alkylenegroup” described above which contains an oxygen atom or a sulfur atom inthe carbon chain or at the end of the carbon chain, and can be, forexample, a —O—CH₂—, —O—(CH₂)₂—, —O—(CH₂)₃—, —O—(CH₂)₄—, —O—(CH₂)₅—,—O—(CH₂)₆—, —O—(CH₂)₇—, —O—(CH₂)₈—, —O—(CH₂)₉—, —O—(CH₂)₁₀—,—CH₂—O—CH₂—, —CH₂—O—(CH₂)₂—, —CH₂—O—(CH₂)₃—, —CH₂—O—(CH₂)₄—,—(CH₂)₂—O—CH₂—, —(CH₂)₂—O—(CH₂)₂—, —(CH₂)₂—O—(CH₂)₃—, —(CH₂)₂—O—(CH₂)₄—,—(CH₂)₃—O—CH₂—, —(CH₂)₃—O—(CH₂)₂—, —(CH₂)₃—O—(CH₂)₃—, —(CH₂)₄—O—CH₂—,—(CH₂)₄—O—(CH₂)₂—, —(CH₂)₅—O—CH₂—, —CH₂—O—, —(CH₂)₂—O—, —(CH₂)₃—O—,—(CH₂)₄—O—, —(CH₂)₅—O—, —(CH₂)₆—O—, —(CH₂)₇—O—, —(CH₂)₈—O—, —(CH₂)₉—O—,—(CH₂)₁₀—O—, —S—CH₂—, —S—(CH₂)₂—, —S—(CH₂)₃—, —S—(CH₂)₄—, —S—(CH₂)₅—,—S—(CH₂)₆—, —S—(CH₂)₇—, —S—(CH₂)₈—, —S—(CH₂)₉—, —S—(CH₂)₁₀—,—CH₂—S—CH₂—, —CH₂—S—(CH₂)₂—, —CH₂—S—(CH₂)₃—, —CH₂—S—(CH₂)₄—,—(CH₂)₂—S—CH₂—, —(CH₂)₂—S—(CH₂)₂—, —(CH₂)₂—S—(CH₂)₃—, —(CH₂)₂—S—(CH₂)₄—,—(CH₂)₃—S—CH₂—, —(CH₂)₃—S—(CH₂)₂—, —(CH₂)₃—S—(CH₂)₃—, —(CH₂)₄—S—CH₂—,—(CH₂)₄—S—(CH₂)₂—, —(CH₂)₅—S—CH₂—, —CH₂—S—, —(CH₂)₂—S—, —(CH₂)₃—S—,—(CH₂)₄—S—, —(CH₂)₅—S—, —(CH₂)₆—S—, —(CH₂)₇—S—, —(CH₂)₈—S—, —(CH₂)₉—S—,or —(CH₂)₁₀—S— group, and is preferably a C₁–C₆ alkylene group whichcontains an oxygen atom in the carbon chain or at the end of the carbonchain, more preferably a —O—CH₂—, —(CH₂)₂—, —O—(CH₂)₃—, —CH₂—O—,—(CH₂)₂—O—, or —(CH₂)₃—O— group, and most preferably a —CH₂—O— or—(CH₂)₂—O— group.

The C₃–C₁₀ cycloalkyl moiety of the “C₃–C₁₀ cycloalkyl group”, the“C₃–C₁₀ cycloalkyl group substituted with from 1 to 3 substituentsselected from Substituent group (a)”, or the “C₃–C₁₀ cycloalkyl groupsubstituted with from 1 to 3 substituents selected from the groupconsisting of Substituent group (a) and Substituent group (b)” in thedefinition of R⁵ or Substituent group (b), may optionally be fused withother cyclic groups, and can be, for example, a group such as acyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,norbornyl, adamantyl, or indanyl group, and is preferably a C₅–C₆cycloalkyl group, and most preferably a cyclohexyl group.

The 5- to 7-membered heterocyclic moiety containing from 1 to 3heteroatoms selected from the group consisting of a sulfur atom, anoxygen atom, and a nitrogen atom in the “5- to 7-membered heterocyclicgroup containing from 1 to 3 heteroatoms selected from the groupconsisting of a sulfur atom, an oxygen atom, and a nitrogen atom”, the“5- to 7-membered heterocyclic group containing from 1 to 3 heteroatomsselected from the group consisting of a sulfur atom, an oxygen atom, anda nitrogen atom in which said heterocyclic group is substituted withfrom 1 to 3 substituents selected from Substituent group (a)”, or the“5- to 7-membered heterocyclic group containing from 1 to 3 heteroatomsselected from the group consisting of a sulfur atom, an oxygen atom, anda nitrogen atom in which said heterocyclic group is substituted withfrom 1 to 3 substituents selected from the group consisting ofSubstituent group (a) and Substituent group (b) in the definition of R⁵or substituent group (b)” can be, for example, a 5- to 7-memberedaromatic heterocyclic or partially or fully hydrogenated saturatedheterocyclic group containing from 1 to 3 heteroatoms selected from thegroup consisting of a sulfur atom, an oxygen atom, and a nitrogen atom.

The heterocyclic group can be a furyl, thienyl, pyrrolyl, azepinyl,pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl,1,2,3-oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyranyl,pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, tetrahydropyranyl,morpholinyl, thiomorpholinyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl,pyrazolidinyl, piperidinyl, piperadinyl, oxazolidinyl, isoxazolidinyl,thiazolidinyl, or pyrazolidinyl group, and is preferably a 5- or6-membered aromatic heterocyclic group, more preferably a furyl,thienyl, or pyrrolyl group, still more preferably a furyl or thienylgroup, and most preferably a thienyl group.

The “aromatic heterocyclic group” described above may optionally befused with other cyclic groups, and can be, for example, a benzothienyl,isobenzofuranyl, chromenyl, xanthenyl, phenoxathiinyl, indolizinyl,isoindolyl, indolyl, indazolyl, purinyl, quinolizinyl, isoquinolyl,quinolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl,carbazolyl, carbolinyl, acridinyl, or isoindolinyl group, and ispreferably a benzothienyl group.

The “halogen atom” in the definition of Substituent group (a) can be afluorine, chlorine, bromine or iodine atom, of which a fluorine orchlorine atom is preferred.

The “lower alkyl group” in the definition of R¹, R², R³, R⁴, orSubstituent group (a) can be, for example, a straight or branched chainalkyl group having from 1 to 6 carbon atoms. Said lower alkyl group canbe, for example, a methyl, ethyl, propyl, isopropyl, butyl, isobutyl,s-butyl, tert-butyl, pentyl, isopentyl, 2-methylbutyl, neopentyl,1-ethylpropyl, hexyl, isohexyl, 4-methylpentyl, 3-methylpentyl,2-methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl,1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl,2,3-dimethylbutyl, 1-ethylbutyl or 2-ethylbutyl group, and is preferablya C₁–C₄ alkyl group, more preferably a C₁–C₂ alkyl group, and mostpreferably a methyl group.

The “halogeno lower alkyl group” in the definition of Substituent group(a) is a group wherein said “lower alkyl group” is substituted with ahalogen atom. Said halogeno lower alkyl group can be, for example, ahalogeno C₁–C₆ alkyl group such as a trifluoromethyl, trichloromethyl,difluoromethyl, dichloromethyl, dibromomethyl, fluoromethyl,2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 2-bromoethyl, 2-chloroethyl,2-fluoroethyl, 2-iodoethyl, 3-chloropropyl, 4-fluorobutyl, 6-iodohexyl,or 2,2-dibromoethyl group, and is preferably a halogeno C₁–C₄ alkylgroup, more preferably a trifluoromethyl, trichloromethyl,2,2,2-trifluoroethyl, or 2,2,2-trichloroethyl group, and most preferablya trifluoromethyl group.

The “lower alkoxy group” in the definition of Substituent group (a) is agroup wherein said “lower alkyl group” is bonded to an oxygen atom. Saidlower alkoxy group can be, for example, a straight or branched chainalkoxy group having from 1 to 6 carbon atoms such as a methoxy, ethoxy,propoxy, isopropoxy, butoxy, isobutoxy, s-butoxy, tert-butoxy, pentoxy,isopentoxy, 2-methylbutoxy, 1-ethylpropoxy,2-ethylpropoxy, neopentoxy,hexyloxy, 4-methylpentoxy, 3-methylpentoxy, 2-methylpentoxy,3,3-dimethylbutoxy, 2,2-dimethylbutoxy, 1,1-dimethylbutoxy,1,2-dimethylbutoxy, 1,3-dimethylbutoxy, or 2,3-dimethylbutoxy group, andis preferably a C₁–C₄ alkoxy group, more preferably a C₁–C₂ alkoxygroup, and most preferably a methoxy group.

The “lower alkylthio group” in the definition of Substituent group (a)is a group wherein said “lower alkyl group” is bonded to a sulfur atom.Said lower alkylthio group can be, for example, a straight or branchedchain alkylthio group having from 1 to 6 carbon atoms such as amethylthio, ethylthio, propylthio, isopropylthio, butylthio,isobutylthio, s-butylthio, tert-butylthio, pentylthio, isopentylthio,2-methylbutylthio, neopentylthio, hexylthio, 4-methylpentylthio,3-methylpentylthio, 2-methylpentylthio, 3,3-dimethylbutylthio,2,2-dimethylbutylthio, 1,1-dimethylbutylthio, 1,2-dimethylbutylthio,1,3-dimethylbutylthio, or 2,3-dimethylbutylthio group, and is preferablya C₁–C₄ alkylthio group, more preferably a C₁–C₂ alkylthio group, andmost preferably a methylthio group.

The “lower alkoxycarbonyl group” in the definition of Substituent group(a) is a group wherein said “lower alkoxy group” is bonded to a carbonylgroup. Said lower alkoxycarbonyl group can be, for example, a straightor branched chain alkoxycarbonyl group having from 1 to 6 carbon atomssuch as a methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, s-butoxycarbonyl,tert-butoxycarbonyl, pentoxycarbonyl, isopentoxycarbonyl,2-methylbutoxycarbonyl, neopentoxycarbonyl, hexyloxycarbonyl,4-methylpentoxycarbonyl, 3-methylpentoxycarbonyl,2-methylpentoxycarbonyl, 3,3-dimethylbutoxycarbonyl,2,2-dimethylbutoxycarbonyl, 1,1-dimethylbutoxycarbonyl,1,2-dimethylbutoxycarbonyl, 1,3-dimethylbutoxycarbonyl, or2,3-dimethylbutoxycarbonyl group, and is preferably a C₁–C₄alkoxycarbonyl group, more preferably a C₁–C₂ alkoxycarbonyl group, andmost preferably a methoxycarbonyl group.

The “lower aliphatic acyl group” in the definition of Substituent group(a) is a group wherein a hydrogen atom or a saturated or unsaturatedaliphatic hydrocarbon group is bonded to a carbonyl group. Said loweraliphatic hydrocarbon group can be, for example, a straight or branchedchain lower aliphatic acyl group having from 1 to 8 carbon atoms such asa formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl,pivaloyl, hexanoyl, acryloyl, methacryloyl, or crotonoyl group, and ispreferably a C₁–C₄ lower aliphatic acyl group, more preferably an acetylor propionyl group, and most preferably an acetyl group.

The “mono lower alkylamino group” in the definition of Substituent group(a) is a group wherein said “lower alkyl group” is bonded to one aminogroup. Said mono lower alkylamino group can be, for example, amono-C₁–C₄ alkylamino group such as a methylamino, ethylamino,propylamino, isopropylamino, butylamino, isobutylamino, s-butylamino,tert-butylamino, pentylamino, isopentylamino, 2-methylbutylamino,neopentylamino, 1-ethylpropylamino, hexylamino, isohexylamino,4-methylpentylamino, 3-methylpentylamino, 2-methylpentylamino,1-methylpentylamino, 3,3-dimethylbutylamino, 2,2-dimethylbutylamino,1,1-dimethylbutylamino, 1,2-dimethylbutylamino, 1,3-dimethylbutylamino,2,3-dimethylbutylamino, or 2-ethylbutylamino group, and is preferably amono-C₁–C₄ alkylamino group, more preferably a mono-C₁–C₂ alkylaminogroup, and most preferably a methylamino group.

The “di-lower alkylamino group” in the definition of Substituent group(a) is a group wherein two said “lower alkyl groups” are bonded to anamino group. Said di-lower alkylamino group can be, for example, adi-C₁–C₆ alkylamino group such as a dimethylamino, diethylamino,N-ethyl-N-methylamino, dipropylamino, dibutylamino, dipentylamino, ordihexylamino group, and is preferably a di-C₁–C₄ alkylamino group, morepreferably a di-C₁–C₂ alkylamino group, and most preferably adimethylamino group.

The “lower aliphatic acylamino group” in the definition of Substituentgroup (a) is a group wherein said “lower aliphatic acyl group” is bondedto an amino group. Said lower aliphatic acylamino group can be, forexample, a straight or branched chain lower aliphatic acylamino grouphaving from 1 to 7 carbon atoms such as a formylamino, acetylamino,propionylamino, butyrylamino, isobutyrylamino, valerylamino,isovalerylamino, pivaloylamino, hexanoylamino, acryloylamino,methacryloylamino, or crotonoylamino group, and is preferably a C₁–C₄lower aliphatic acylamino group, more preferably an acetylamino orpropionylamino group, and most preferably an acetylamino group.

The “lower alkylsulfonyl group” in the definition of D is a groupwherein said “lower alkyl group” is bonded to a sulfonyl group. Saidlower alkylsulfonyl group can be, for example, a straight or branchedchain alkylsulfonyl group having from 1 to 6 carbon atoms such as amethanesulfonyl, ethanesulfonyl, propanesulfonyl, isopropanesulfonyl,butanesulfonyl, isobutanesulfonyl, s-butanesulfonyl,tert-butanesulfonyl, pentanesulfonyl, isopentanesulfonyl,2-methylbutanesulfonyl, neopentanesulfonyl, hexanesulfonyl,4-methylpentanesulfonyl, 3-methylpentanesulfonyl,2-methylpentanesulfonyl, 3,3-dimethylbutanesulfonyl,2,2-dimethylbutanesulfonyl, 1,1-dimethylbutanesulfonyl,1,2-dimethylbutanesulfonyl, 1,3-dimethylbutanesulfonyl, or2,3-dimethylbutanesulfonyl group, and is preferably a C₁–C₄alkylsulfonyl group, more preferably a C₁–C₂ alkylsulfonyl group, andmost preferably a methanesulfonyl group.

The “arylsulfonyl group” in the definition of D is a group wherein said“aryl group” is bonded to a sulfonyl group. Said arylsulfonyl group canbe, for example, an arylsulfonyl group having from 6 to 10 carbon atomssuch as a benzenesulfonyl, p-toluenesulfonyl, o-xylene-4-sulfonyl,m-xylene-4-sulfonyl, p-xylenesulfonyl, or naphthalenesulfonyl group, andis preferably a benzenesulfonyl group.

The “protecting group of the amino group” in the definitions of R¹ andR² is a protecting group for an amino group which is generally used inthe field of synthetic organic chemistry, and can be:

an “aliphatic acyl group”, for example, a “lower aliphatic acyl group”described above, a halogeno lower aliphatic acyl group such as achloroacetyl, dichloroacetyl, trichloroacetyl, or trifluoroacetyl group,or a lower aliphatic acyl group substituted with a lower alkoxy such asa methoxyacetyl group;

an “aromatic acyl group”, for example, an aromatic acyl group such as abenzoyl, 1-indanecarbonyl, 2-indanecarbonyl, or 1- or 2-naphthoyl group,or an aromatic acyl group substituted with from 1 to 3 substituentsselected from Substituent group (a) described above such as a4-chlorobenzoyl, 4-fluorobenzoyl, 2,4,6-trimethylbenzoyl, 4-toluoyl,4-anisoyl, 4-nitrobenzoyl, 2-nitrobenzoyl, 2-(methoxycarbonyl)benzoyl,or 4-phenylbenzoyl group;

an “alkoxycarbonyl group”, for example, a “lower alkoxycarbonyl group”described above, or a lower alkoxycarbonyl group substituted with one ormore halogen atoms or one or more tri-lower alkylsilyl groups such as a2,2,2-trichloroethoxycarbonyl or 2-trimethylsilylethoxycarbonyl group;

an “alkenyloxycarbonyl group” such as a vinyloxycarbonyl orallyloxycarbonyl group;

an “aralkyloxycarbonyl group”, for example, an aralkyloxycarbonyl groupsuch as a benzyloxycarbonyl group, or an aralkyloxycarbonyl groupsubstituted with 1 to 3 substituents selected from Substituent group (a)described above such as a 4-methoxybenzyloxycarbonyl,3,4-dimethoxybenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl, or4-nitrobenzyloxycarbonyl group;

a “silyl group”, for example, a tri-lower alkylsilyl group such as atrimethylsilyl, triethylsilyl, isopropyldimethylsilyl,tert-butyldimethylsilyl, methyldiisopropylsilyl,methyldi(tert-butyl)silyl, or triisopropylsilyl group, or a silyl groupsubstituted with 3 substituents selected from aryl groups or aryl groupsand lower alkyl groups such as a diphenylmethylsilyl,diphenylbutylsilyl, diphenylisopropylsilyl, or phenyldiisopropylsilylgroup;

an “aralkyl group”, for example, a lower alkyl group substituted withfrom 1 to 3 aryl groups such as a benzyl, phenethyl, 3-phenylpropyl,α-naphthylmethyl, β-naphthylmethyl, diphenylmethyl, triphenylmethyl,α-naphthyldiphenylmethyl, or 9-anthrylmethyl group, or a lower alkylgroup substituted with from 1 to 3 aryl groups, wherein said aryl groupis substituted with a lower alkyl group, a lower alkoxy group, a nitrogroup, a halogen atom, or a cyano group, such as a 4-methylbenzyl,2,4,6-trimethylbenzyl, 3,4,5-trimethylbenzyl, 4-methoxybenzyl,4-methoxyphenyldiphenylmethyl, 2-nitrobenzyl, 4-nitrobenzyl,4-chlorobenzyl, 4-bromobenzyl, 4-cyanobenzyl,4-cyanobenzyldiphenylmethyl, bis(2-nitrophenyl)methyl, or piperonylgroup; or

a “substituted methylene group forming a Schiff base” such as aN,N-dimethylaminomethylene, benzylidene, 4-methoxybenzylidene,4-nitrobenzylidene, salicylidene, 5-chlorosalicylidene,diphenylmethylene, or (5-chloro-2-hydroxyphenyl)phenylmethylene group.

The “protecting group of the amino group” is preferably a loweraliphatic acyl group, a lower alkoxycarbonyl group, anaralkyloxycarbonyl group, or an aralkyloxycarbonyl group substitutedwith from 1 to 3 substituents selected from Substituent group (a),particularly preferably an acetyl or tert-butoxycarbonyl group.

The “protecting group of the hydroxyl group” in the definition of R³represents a “general protecting group in chemical reactions” which canbe cleaved by a chemical process such as hydrogenolysis, hydrolysis,electrolysis, and photolysis, or a “protecting group which can becleaved by a biological process such as hydrolysis in vivo”.

The “general protecting group in chemical reactions” can be, forexample,

an “aliphatic acyl group” described above;

an “aromatic acyl group” described above;

a “tetrahydropyranyl or tetrahydrothiopyranyl group” such as atetrahydropyran-2-yl, 3-bromotetrahydropyran-2-yl,4-methoxytetrahydropyran-4-yl, tetrahydrothiopyran-2-yl, or4-methoxytetrahydrothiopyran-4-yl group;

a “tetrahydrofuranyl or tetrahydrothiofuranyl group” such as atetrahydrofuran-2-yl or tetrahydrothiofuran-2-yl group;

a “silyl group” described above;

an “alkoxymethyl group”, for example, a lower alkoxymethyl group such asa methoxymethyl, 1,1-dimethyl-1-methoxymethyl, ethoxymethyl,propoxymethyl, isopropoxymethyl, butoxymethyl, or tert-butoxymethylgroup, a lower alkoxylated lower alkoxymethyl group such as a2-methoxyethoxymethyl group, or a halogeno lower alkoxymethyl group suchas a 2,2,2-trichloroethoxymethyl or bis(2-chloroethoxy)methyl group;

a “substituted ethyl group”, for example, a lower alkoxylated ethylgroup such as a 1-ethoxyethyl or 1-(isopropoxy)ethyl group, or ahalogenated ethyl group such as a 2,2,2-trichloroethyl group;

an “aralkyl group” described above;

an “alkoxycarbonyl group” described above;

an “alkenyloxycarbonyl group” described above; or

an “aralkyloxycarbonyl group” described above.

On the other hand, the “protecting group which can be cleaved by abiological process such as hydrolysis in vivo” can be, for example,

-   -   a “carbonyloxyalkyl group”, for example,        -   an acyloxyalkyl group such as an ethylcarbonyloxymethyl,            pivaloyloxymethyl, dimethylaminoacetoxymethyl, or            1-acetoxyethyl group;        -   a 1-(alkoxycarbonyloxy)alkyl group such a            1-(methoxycarbonyloxy)ethyl, 1-(ethoxycarbonyloxy)ethyl,            ethoxycarbonyloxymethyl, 1-(isopropoxycarbonyloxy)ethyl,            1-(tert-butoxycarbonyloxy)ethyl,            1-(ethoxycarbonyloxy)propyl, or            1-(cyclohexyloxycarbonyloxy)ethyl group;        -   a phthalidyl group; or        -   an oxodioxolenylmethyl group such as a            4-methyl-oxodioxolenylmethyl, 4-phenyl-oxodioxolenylmethyl,            or oxodioxolenylmethyl group;    -   an “aliphatic acyl group” described above;    -   an “aromatic acyl group” described above;    -   “residual group of a succinic acid half-ester”;    -   a “residual group of a phosphoric acid ester”;    -   a “residual group forming an amino acid ester or the like”;    -   a carbamoyl group;    -   a “protecting group of two hydroxyl groups”, for example, an        aralkylidene group such as a benzylidene group, an        alkoxyethylidene group such as a methoxyethylidene or        ethoxyethylidene group, an oxomethylene group, or a        thioxomethylene group; or    -   a “carbonyloxyalkyloxycarbonyl group” such as a        pivaloyloxymethyloxycarbonyl group.

The suitability of such a derivative can be determined by administeringit to an experimental animal such as a rat or a mouse by an intravenousinjection, measuring a body fluid of the animal thereafter and detectingthe original compound or a pharmacologically acceptable salt thereof.

The “protecting group of the hydroxyl group” is preferably a loweraliphatic acyl group, an aromatic acyl group, an aromatic acyl groupsubstituted with from 1 to 3 substituents selected from Substituentgroup (a), or a silyl group, particularly preferably an acetyl group ora tert-butyldimethylsilyl group.

The “protecting group of phosphoric acid” in the definition of R¹⁰ orR¹¹ can be, for example,

-   -   a lower alkyl group such as a methyl, ethyl, isopropyl, or butyl        group,    -   a lower alkyl group substituted with one or more cyano groups        such as a 2-cyanoethyl or 2-cyano-1,1-dimethylethyl group,    -   a lower alkyl group substituted with one or more silyl groups        wherein said silyl group is substituted with 3 substituents        selected from the group consisting of lower alkyl groups or aryl        groups and lower alkyl groups such as a        2-(methyldiphenylsilyl)ethyl or 2-trimethylsilylethyl group,    -   a lower alkyl group substituted with one or more heterocyclyl        groups such as a 2-(2′-pyridyl)ethyl or 2-(4′-pyridyl)ethyl        group,    -   a lower alkyl group substituted with one or more arylthio groups        such as a 2-phenylthioethyl, 2-(4′-nitrophenylthio)ethyl, or        2-(4′-triphenylmethylphenylthio)ethyl group,    -   a lower alkyl group substituted with one or more alkylsulfonyl        groups, arylsulfonyl groups, or arylalkylsulfonyl groups such as        a 2-(tert-butylsulfonyl)ethyl, 2-(phenylsulfonyl)ethyl, or        2-(benzylsulfonyl)ethyl group, or    -   a halogeno lower alkyl group such as a 2,2,2trichloroethyl,        2,2,2-trichloroethyl-1,1-dimethylethyl, 2,2,2-tribromoethyl,        2,3-dibromopropyl, or 2,2,2-trifluoroethyl group;

an aralkyl group, for example,

-   -   a lower alkyl group substituted with from 1 to 3 aryl groups,        such as a benzyl, phenethyl, 3-phenylpropyl, α-naphthylmethyl,        β-naphthylmethyl, diphenylmethyl, triphenylmethyl,        α-naphthyldiphenylmethyl, or 9-anthrylmethyl group,    -   a lower alkyl group substituted with one or more aryl groups        wherein said aryl moiety is substituted with one or more nitro        groups, halogen atoms, or lower aliphatic acyl groups, such as        an o-nitrobenzyl, 4-nitrobenzyl, 2,4-dinitrobenzyl,        4-chlorobenzyl, 4-chloro-2-nitrobenzyl, or 4-acyloxybenzyl        group,    -   a lower alkyl group substituted with one or more aryl groups        having one or more substituents such as a 2-nitrophenylethyl        group, or    -   a lower alkyl group substituted with one or more fluorenyl        groups such as a 9-fluorenylmethyl group;

a lower alkenyl group such as an allyl or propenyl group;

a lower alkenyl group substituted with one or more cyano groups such asa 4-cyano-2-butenyl group;

an aryl group such as a phenyl group;

an aryl group substituted with one or more substituents selected fromthe group consisting of a lower alkyl group, a lower alkyl groupsubstituted with 3 aryl groups, a lower alkoxy group, a nitro group, anda halogen atom, such as a 2-methylphenyl, 2,6-dimethylphenyl,2-chlorophenyl, 4-chlorophenyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl,2,6-dichlorophenyl, 2-bromophenyl, 4-nitrophenyl, 3,5-dinitrophenyl,4-chloro-2-nitrophenyl, or 2-methoxy-5-nitrophenyl group; or

an amide such as an anilidate, 4-triphenylmethylanilidate,[N-(2-trityloxy)ethyl]anilidate, p-(N,N-dimethylamino)anilidate, or3-(N,N-diethylaminomethyl)anilidate.

The “protecting group of phosphoric acid” is preferably a lower alkylgroup, a lower alkenyl group, or a methyl group substituted with from 1to 3 substituents selected from the group consisting of a phenyl groupand a naphthyl group, more preferably a methyl group, an ethyl group, anallyl group, or a benzyl group, and most preferably a methyl group or anethyl group.

The “C₃–C₁₀ cycloalkyl group substituted with from 1 to 3 substituentsselected from the group consisting of Substituent group (a) andSubstituent group (b)” in the definition of R⁵ can be, for example, a2-fluorocyclopropyl, 2-chlorocyclopropyl, 2- or 3-fluorocyclopentyl, 2-or 3-chlorocyclopentyl, 2-,3- or 4-fluorocyclohexyl, 2-,3- or4-chlorocyclohexyl, 2-,3- or 4-bromocyclohexyl, 2-,3- or4-iodocyclohexyl, 2-methylcyclopropyl, 2-ethylcyclopropyl, 2- or3-methylcyclopentyl, 2- or 3-ethylcyclopentyl, 2-,3- or4-methylcyclohexyl, 2-,3- or 4-ethylcyclohexyl,2-trifluoromethylcyclopropyl, 2- or 3-trifluoromethylcyclobutyl, 2- or3-trifluoromethylcyclopentyl, 2-,3- or 4-trifluoromethylcyclohexyl,2-methoxycyclopropyl, 2- or 3-methoxycyclobutyl, 2- or3-methoxycyclopentyl, 2-, 3- or 4-methoxycyclohexyl, 2-,3- or4-ethoxycyclohexyl, 2-,3- or 4-propoxycyclohexyl, 2-,3- or4-isopropoxycyclohexyl, 2-,3- or 4-(1-ethylpropoxy)cyclohexyl, 2-,3- or4-(2-ethylpropoxy)cyclohexyl, 2-carboxycyclopropyl, 2- or3-carboxycyclopentyl, 2-,3- or 4-carboxycyclohexyl,2-methoxycarbonylcyclopropyl, 2- or 3-methoxycarbonylcyclopentyl, 2-,3-or 4-methoxycarbonylcyclohexyl, 2-hydroxycyclopropyl, 2- or3-hydroxycyclopentyl, 2-,3- or 4-hydroxycyclohexyl, 2-formylcyclopropyl,2- or 3-formylcyclopentyl, 2-,3- or 4-formylcyclohexyl,2-acetylcyclopropyl, 2- or 3-acetylcyclopentyl, 2-,3- or4-acetylcyclohexyl, 2-aminocyclopropyl, 2- or 3-aminocyclopentyl, 2-,3-or 4-aminocyclohexyl, 2-methylaminocyclopropyl, 2- or3-methylaminocyclobutyl, 2- or 3-methylaminocyclopentyl, 2-,3- or4-methylaminocyclohexyl, 2-dimethylaminocyclopropyl, 2- or3-dimethylaminocyclobutyl, 2- or 3-dimethylaminocyclopentyl, 2-,3- or4-dimethylaminocyclohexyl, 2-cyanocyclopropyl, 2- or 3-cyanocyclopentyl,2-,3- or 4-cyanocyclohexyl, 2- or 3-cyclohexylcyclopentyl, 2-,3- or4-cyclohexylcyclohexyl, 2-phenylcyclopropyl, 2- or 3-phenylcyclopentyl,2-,3- or 4-phenylcyclohexyl, 3,4-difluorocyclohexyl,3,4-dichlorocyclohexyl, 2,3-dimethoxycyclohexyl,3,4-dimethoxycyclohexyl, 3,5-dimethoxycyclohexyl, or3,4,5-trimethoxycyclohexyl group, and is preferably a C₃–C₁₀ cycloalkylgroup substituted with from 1 to 3 substituents (said substituent(s)being selected from the group consisting of halogen atoms, lower alkylgroups, halogeno lower alkyl groups, lower alkoxy groups, loweralkylthio groups, and lower aliphatic acyl groups), more preferably aC₃–C₁₀ cycloalkyl group substituted with from 1 to 3 substituents (saidsubstituent(s) being selected from the group consisting of halogenatoms, lower alkyl groups, halogeno lower alkyl groups, lower alkoxygroups, and lower aliphatic acyl groups), still more preferably a C₃–C₁₀cycloalkyl group substituted with from 1 to 3 substituents (saidsubstituent(s) being selected from the group consisting of halogenatoms, lower alkyl groups, halogeno lower alkyl groups, lower alkoxygroups, and lower aliphatic acyl groups), and most preferably acyclohexyl group substituted with one substituent (said substituent isselected from the group consisting of a fluorine atom, a chlorine atom,methyl, trifluoromethyl, methoxy and acetyl groups).

The “C₆–C₁₀ aryl group substituted with from 1 to 3 substituentsselected from the group consisting of Substituent group (a) andSubstituent group (b)” in the definition of R⁵ can be, for example, a2-,3- or 4-fluorophenyl, 2-,3- or 4-chlorophenyl, 2-,3- or4-bromophenyl, 2-,3- or 4-iodophenyl, 2-,3- or 4-methylphenyl, 2-,3- or4-ethylphenyl, 2-,3- or 4-propylphenyl, 2-,3- or 4-butylphenyl, 2-,3- or4-pentylphenyl, 2-,3- or 4-trifluoromethylphenyl, 2-,3- or4-methoxyphenyl, 2-,3- or 4-ethoxyphenyl, 2-,3- or 4-propoxyphenyl,2-,3- or 4-isopropoxyphenyl, 2-,3- or 4-butoxyphenyl, 2-,3- or4-(1-ethylpropoxy)phenyl, 2-,3- or 4-(2-ethylpropoxy)phenyl, 2-,3- or4-methylthiophenyl, 2-,3- or 4-ethylthiophenyl, 2-,3- or4-carboxyphenyl, 2-,3- or 4-methoxycarbonylphenyl, 2-,3- or4-ethoxycarbonylphenyl, 2-,3- or 4-hydroxyphenyl, 2-,3- or4-formylphenyl, 2-,3- or 4-acetylphenyl, 2-,3- or 4-aminophenyl, 2-,3-or 4-methylaminophenyl, 2-,3- or 4-dimethylaminophenyl, 2-,3- or4-cyanophenyl, 2-,3- or 4-cyclopentylphenyl, 2-,3- or4-cyclohexylphenyl, 2-,3- or 4-biphenyl, 2,4-difluorophenyl,3,4-difluorophenyl, 3,5-difluorophenyl, 2,4-dichlorophenyl,3,4-dichlorophenyl, 3,5-dichlorophenyl, 3,4-dibromophenyl,2,3-dimethylphenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl,2,3-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl,3,4,5-trimethoxyphenyl, 3-fluoro-4-methoxyphenyl,4-methyl-2-methoxyphenyl, 6-fluoro-4-methyl-2-methoxyphenyl,5-fluoroinden-3-yl, 5-methylinden-3-yl, 5-methoxyinden-3-yl,5-fluoroinden-2-yl, 5-chloroinden-2-yl, 5-methylinden-2-yl,5-methoxyinden-2-yl, 5-hydroxyinden-3-yl, 5-nitroinden-3-yl,5-cyclohexylinden-3-yl, 5-phenylinden-3-yl, 5-phenoxyinden-3-yl,5-benzyloxyinden-3-yl, 5-phenylthioinden-3-yl, 5-hydroxyinden -2-yl,5-nitroinden-2-yl, 5-cyclohexylinden-2-yl, 5-phenylinden-2-yl,5-fluoronaphthalen-2-yl, 5-methylnaphthalen-2-yl,5-methoxynaphthalen-2-yl, 5-fluoronaphthalen-1-yl,5-methylnaphthalen-1-yl, 5-methoxynaphthalen-1-yl,5-hydroxynaphthalen-2-yl, 5-nitronaphthalen-2-yl,5-cyclohexylnaphthalen-2-yl, 5-phenylnaphthalen-2-yl,5-phenoxynaphthalen-2-yl, 5-benzyloxynaphthalen-2-yl,5-phenylthionaphthalen-2-yl, 5-hydroxynaphthalen-1-yl,5-nitronaphthalen-1-yl, 5-cyclohexylnaphthalen-1-yl, or5-phenylnaphthalen-1-yl group, and is preferably a C₆–C₁₀ aryl groupsubstituted with from 1 to 3 substituents (said substituent(s) beingselected from the group consisting of halogen atoms, lower alkyl groups,halogeno lower alkyl groups, lower alkoxy groups, a lower alkylthiogroups, and lower aliphatic acyl groups), more preferably a C₆–C₁₀ arylgroup substituted with from 1 to 3 substituents (said substituent(s)being selected from the group consisting of halogen atoms, lower alkylgroups, halogeno lower alkyl groups, lower alkoxy groups, and loweraliphatic acyl groups), still more preferably a phenyl group substitutedwith from 1 to 3 substituents (said substituent(s) being selected fromthe group consisting of halogen atoms, lower alkyl groups, halogenolower alkyl groups, lower alkoxy groups, and lower aliphatic acylgroups), particularly preferably a phenyl group substituted with 1 or 2substituents (said substituent(s) being selected from the groupconsisting of fluorine atoms, chlorine atoms, methyl, trifluoromethyl,methoxy and acetyl groups; but, in the case of methoxy group, a phenylgroup substituted with from 1 to 3 methoxy groups is preferred), andmost preferably a 3-fluorophenyl, 4-fluorophenyl, 3,4-difluorophenyl,3,5-difluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,4-dichlorophenyl,3,5-dichlorophenyl, 3-methylphenyl, 4-methylphenyl, 3,4-dimethylphenyl,3,5-dimethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl,3,4-ditrifluoromethylphenyl, 3,5-ditrifluoromethylphenyl,3-methoxyphenyl, 4-methoxyphenyl, 3,4-dimethoxyphenyl,3,5-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 3-acetylphenyl, or4-acetylphenyl group.

The “5- to 7-membered heterocyclic group containing from 1 to 3heteroatoms selected from the group consisting of a sulfur atom, anoxygen atom, and a nitrogen atom in which said heterocyclic group issubstituted with from 1 to 3 substituents selected from the groupconsisting of Substituent group (a) and Substituent group (b)” in thedefinition of R⁵ can be, for example, a 3-,4- or 5-methylfuran-2-yl,2-,4- or 5-methylfuran-3-yl, 3-,4- or 5-fluorothiophen-2-yl, 2-,4- or5-fluorofuran-3-yl, 3-,4- or 5-bromothiophen-2-yl, 2-,4- or5-bromofuran-3-yl, 3-,4- or 5-methylthiophen-2-yl, 2-,4- or5-methylthiophen-3-yl, 3-,4- or 5-ethylthiophen-2-yl, 2-,4- or5-ethylthiophen-3-yl, 3-,4- or 5-methoxythiophen-2-yl, 2-,4- or5-methoxythiophen-3-yl, 3- or 4-methylthiazol-5-yl, 3-,4- or5-fluorobenzothiophen-2-yl, 3-,4- or 5-bromobenzothiophen-2-yl, 3-,4- or5-methylbenzothiophen-2-yl, 3-,4- or 5-methoxybenzothiophen-2-yl, 2-,4-or 5-fluorobenzothiophen-3-yl, 2-,4- or 5-bromobenzothiophen-3-yl, 2-,4-or 5-methylbenzothiophen-3-yl, 2-,4- or 5-methoxybenzothiophen-3-yl,4-,5-,6- or 7-methylbenzothiophen-2-yl, 3-,4- or 5-hydroxyfuran-2-yl,2-,4- or 5-hydroxyfuran-3-yl, 3-,4- or 5-hydroxythiophen-2-yl, 3-,4- or5-nitrothiophen-2-yl, 3-,4- or 5-phenylthiophen-2-yl, 2-,4- or5-hydroxythiophen-3-yl, 2-,4-or 5-cyanothiophen-3-yl, 1-,2- or3-hydroxypyridin-4-yl, 1-,2- or 3-cyanopyridin-4-yl, or 1-,2- or3-phenylpyridin-4-yl group, and is preferably a 3-,4- or5-fluorothiophen-2-yl or 2-,4- or 5-fluorofuran-3-yl group.

The “pharmacologically acceptable salt thereof” means a salt which, whenthe compounds of general formula (I), (II), or (III) of the presentinvention have a basic group such as an amino group, can be prepared byreacting the compounds with an acid, and when the compounds of generalformula (I), (II), or (III) of the present invention have an acidicgroup such as a carboxyl group or a phosphate group, can be prepared byreacting the compounds with a base. Such salts are included in thepresent invention.

The salt, when the compounds of general formula (I), (II), or (III) havea basic group, can be an inorganic acid salt, for example, a hydrohalidesuch as hydrofluoride, hydrochloride, hydrobromide, or hydroiodide, anitrate, a perchlorate, a sulfate, a phosphate or the like; an organicacid salt, for example, a lower alkanesulfonate such asmethanesulfonate, trifluoromethanesulfonate, or ethanesulfonate, anarylsulfonate such as benzenesulfonate or p-toluenesulfonate, anacetate, a malate, a fumarate, a succinate, a citrate, an ascorbate, atartrate, an oxalate, a maleate, or the like; or an amino acid salt suchas glycine salt, lysine salt, arginine salt, ornithine salt, glutamicacid salt, or aspartic acid salt. The salt is preferably an organic acidsalt (particularly fumarate, oxalate or maleate) or a hydrohalide(particularly hydrochloride).

The salt, when the compounds of general formula (I), (II), or (III) havean acidic group, can be a metal salt, for example, an alkali metal saltsuch as sodium salt, potassium salt, or lithium salt, an alkaline earthmetal salt such as calcium salt or magnesium salt, an aluminum salt, aniron salt, or the like; an amine salt, for example, an inorganic aminesalt such as ammonium salt, an organic amine salt such as t-octylaminesalt, dibenzylamine salt, morpholine salt, glucosamine salt,phenylglycine alkyl ester salt, ethylenediamine salt, N-methylglucaminesalt, guanidine salt, diethylamine salt, triethylamine salt,dicyclohexylamine salt, N,N′-dibenzylethylenediamine salt,chloroprocaine salt, procaine salt, diethanolamine salt,N-benzylphenethylamine salt, piperazine salt, tetramethylammonium salt,tris(hydroxymethyl)aminomethane salt, or the like; or an amino acid saltsuch as glycine salt, lysine salt, arginine salt, ornithine salt,glutamic acid salt, or aspartic acid salt. The salt preferably is analkali metal salt (particularly sodium salt).

When the compounds of general formula (I), (II), or (III),pharmacologically acceptable salts thereof, or pharmacologicallyacceptable esters thereof of the present invention are allowed to standin contact with the atmosphere or to recrystallize, they may absorbwater or water may attach to them to form a hydrate. The presentinvention encompasses such hydrates.

The compounds of general formula (I), (II), or (III), pharmacologicallyacceptable salts, or pharmacologically acceptable esters thereof of thepresent invention have one or more asymmetric carbon atoms in theirstructures, and can exist as optical isomers due to such asymmetriccarbon atoms. In the present invention, a single optical isomer andmixtures of optical isomers are represented as a single chemical formula(I), (II), or (III) individually. The present invention encompasses bothindividual optical isomers and mixtures thereof in any ratio. In thecompounds as shown in formulas (I), (II) and (III), the preferredcompounds are compounds in which the asymmetric carbon atom to which theformula -NR¹R² attaches, is the R configuration.

The “ester thereof” described above indicates an ester of compounds ofgeneral formula (I), (II), or (III) of the present invention which havea group capable of being esterified. The ester can be an “ester of ahydroxyl group” or an “ester of a carboxyl group”. Each ester residualgroup belongs to a “general protecting group in chemical reactions” or a“protecting group which can be cleaved by a biological process such ashydrolysis in vivo”.

The “general protecting group in chemical reactions” is a protectinggroup which can be cleaved by a chemical process such as hydrogenolysis,hydrolysis, electrolysis, and photolysis.

The “general protecting group in chemical reactions” and the “protectinggroup which can be cleaved by a biological process such as hydrolysis invivo” related to the “ester of a hydroxyl group” have the same meaningsas those described above for the “protecting group of the hydroxylgroup”.

The “general protecting group in chemical reactions” related to the“ester of a carboxyl group” is preferably a “lower alkyl group”described above; a lower alkenyl group such as ethenyl, 1-propenyl,2-propenyl, 1-methyl-2-propenyl, 1-methyl-1-propenyl,2-methyl-1-propenyl, 2-methyl-2-propenyl, 2-ethyl-2-propenyl, 1-butenyl,2-butenyl, 1-methyl-2-butenyl, 1-methyl-1-butenyl, 3-methyl-2-butenyl,1-ethyl-2-butenyl, 3-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl,1-ethyl-3-butenyl, 1-pentenyl, 2-pentenyl, 1-methyl-2-pentenyl,2-methyl-2-pentenyl, 3-pentenyl, 1-methyl-3-pentenyl,2-methyl-3-pentenyl, 4-pentenyl, 1-methyl-4-pentenyl,2-methyl-4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, or5-hexenyl; a lower alkynyl group such as ethynyl, 2-propynyl,1-methyl-2-propynyl, 2-butynyl, 1-methyl-2-butynyl, 1-ethyl-2-butynyl,3-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 1-ethyl-3-butynyl,2-pentynyl, 1-methyl-2-pentynyl, 3-pentynyl, 1-methyl-3-pentynyl,2-methyl-3-pentynyl, 4-pentynyl, 1-methyl-4-pentynyl,2-methyl-4-pentynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, or 5-hexynyl; a“halogeno lower alkyl group” described above; a hydroxy “lower alkylgroup” such as 2-hydroxyethyl, 2,3-dihydroxypropyl, 3-hydroxypropyl,3,4-dihydroxybutyl, or 4-hydroxybutyl; a “lower aliphatic acyl”-“loweralkyl group” such as acetylmethyl; an “aralkyl group” described above;or a “silyl group” described above.

The “protecting group which can be cleaved by a biological process suchas hydrolysis in vivo” related to the “ester of a carboxyl group” ispreferably an “alkoxyalkyl group” such as a lower alkoxy lower alkylgroup, e.g., methoxyethyl, 1-ethoxyethyl, 1-methyl-1-methoxyethyl,1-(isopropoxy)ethyl, 2-methoxyethyl, 2-ethoxyethyl, ethoxymethyl,n-propoxymethyl, isopropoxymethyl, n-butoxymethyl, or t-butoxymethyl, alower alkoxylated lower alkoxy lower alkyl group, e.g.,2-methoxyethoxymethyl, an “aryl” oxy “lower alkyl group”, e.g.,phenoxymethyl, or a halogenated lower alkoxy lower alkyl group, e.g.,2,2,2-trichloroethoxymethyl or bis(2-chloroethoxy)methyl; a “loweralkoxy” carbonyl “lower alkyl group” such as methoxycarbonylmethyl; acyano “lower alkyl group” such as cyanomethyl or 2-cyanoethyl; a “loweralkyl” thiomethyl group such as methylthiomethyl or ethylthiomethyl; an“aryl” thiomethyl group such as phenylthiomethyl or naphthylthiomethyl;a “lower alkyl” sulfonyl “lower alkyl group” which may be substitutedwith one or more halogen atoms such as 2-methanesulfonylethyl or2-trifluoromethanesulfonylethyl; an “aryl” sulfonyl “lower alkyl group”such as 2-benzenesulfonylethyl or 2-toluenesulfonylethyl; a1-(acyloxy)“lower alkyl group” described above; a “phthalidyl group”described above; an “aryl group” described above; a “lower alkyl group”described above; a “carboxyalkyl group” such as carboxymethyl; or an“amide forming residual group of an amino acid” such as phenylalanine.

The more preferred “general protecting group in chemical reactions” and“protecting group which can be cleaved by a biological process such ashydrolysis in vivo” related to the “ester of a carboxyl group” describedabove is a lower alkyl or aralkyl group.

“Immunosuppressants”, which are an active ingredient of pharmaceuticalcompositions of the present invention, are agents preventing orinhibiting the progression of immune responses as well as compounds withimmunosuppressive activity, and are classified into the following groupson the basis of mechanism of action:

(1) agents which have the action of inhibiting intracellular signaltransduction involved in cytokine expression of T-cells, include thoseblocking cytokine production as well as those preventing cytokinesignaling from acting on immune cells by inhibiting the intracellularsignal transduction. Such agents, which have the action of inhibitingthe intracellular signal transduction involved in cytokine expression ofT-cells, include, for example, S7481/F-1 or a pharmacologicallyacceptable salt thereof disclosed in the specification of U.S. Pat. No.4,117,118 [preferably cyclosporin A, of which the chemical name iscyclo[3-hydroxy-4-methyl-2-(methylamino)-6-octenoyl]-2-aminobutyryl-methylglycyl-methyl-leucyl-valyl-methyl-leucyl-alanyl-alanyl-methyl-leucyl-methyl-leucyl-methyl-valyl.],

a compound having the general formula (I) or a pharmacologicallyacceptable salt thereof disclosed in the specification of E.P.Publication Number 184,162 {preferably tacrolimus, of which the chemicalname is17-allyl-1,14-dihydroxy-12-[2-(4-hydroxy-3-methoxycyclohexyl)-1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0^(4,9)]octacos-18-ene-2,3,10,16-tetrone.},

rapamycin disclosed in the specification of U.S. Pat. No. 3,929,992 [ofwhich the chemical name is9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-hexadecahydro-9,27-dihydroxy-3-[2-(4-hydroxy-3-methoxycyclohexyl)-1-methylethyl]-10,21-dimethoxy-6,18,12,14,20,26-hexamethyl-23,27-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone.],

a compound having the general formula (II) or a pharmacologicallyacceptable salt thereof disclosed in the specification of E.P.Publication Number 94,632 (Japanese Patent Publication (Kokai) NumberSho 58-62152) [preferably gusperimus, of which the chemical name isN-[4-(3-aminopropyl)aminobutyl]carbamoylhydroxymethyl-7-guanidinoheptanamide,and in the present invention gusperimus includes a pharmacologicallyacceptable salt (trihydrochloride) thereof.],

a compound having the general formula (I) or a pharmacologicallyacceptable salt thereof disclosed in the specification of U.S. Pat. No.5,912,253 {preferably everolimus, of which the chemical name is9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-hexadecahydro-9,27-dihydroxy-3-[2-[4-hydroxyethoxy-3-methoxycyclohexyl]-1-methylethyl]-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-23,27-epoxy-3H-pyrido[2,1-c][1,4]azacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone.},

a compound having the general formula (I) or a pharmacologicallyacceptable salt thereof disclosed in the specification of E.P.Publication Number 600,762 {preferably tresperimus, of which thechemical name is2-[4-(3-aminopropylamino)butyl]aminocarbonyloxy-N-[6-(aminoiminomethyl)aminohexyl]acetamide,and in the present invention tresperimus includes a pharmacologicallyacceptable salt thereof.},

LF15-0195 disclosed in Int. J. Immunopharmacol., vol. 21 (5), 349-358(1999) {anisperimus, of which the chemical name is[(6-guanidinohexyl)carbamoyl]methyl[4-(3-aminobutyl)aminobutyl]carbamate.},

a compound having the general formula (I) or a pharmacologicallyacceptable salt thereof disclosed in the specification of E.P.Publication Number 626,385 (Japanese Patent Number 3076724 or U.S. Pat.No. 5,493,019) {preferably SDZ-281-240, of which the chemical name is17-ethyl-1,14-dihydroxy-12-[2-(4-hydroxy-3-methoxycyclohexyl)-1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0^(4,9)]octacos-18-ene-2,3,10,16-tetrone,and in the present invention SDZ-281-240 includes a pharmacologicallyacceptable salt thereof.},

a compound having the general formula (VII) or a pharmacologicallyacceptable salt thereof disclosed in the specification of WO PublicationNumber 93/04680 (E.P. Publication Number 642,516) {preferably ABT-281,of which the chemical name is17-ethyl-1,14-dihydroxy-12-[2-(4-tetrazolyl-3-methoxycyclohexyl)-1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0^(4,9)]octacos-18-ene-2,3,10,16-tetrone.},

a compound having the general formula (A) or a pharmacologicallyacceptable salt thereof disclosed in the specification of E.P.Publication Number 414,632 {preferably tigderimus, of which the chemicalname iscyclo[[3-hydroxy-4-methyl-2-(methylamino)-6-octenoyl]-L-2-aminobutyryl-N-methylglycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl-L-alanyl-[3-O-(2-hydroxyethyl)-D-seryl]-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-1-valyl.],

a compound having the general formula (I) or a pharmacologicallyacceptable salt thereof disclosed in the specification of WO PublicationNumber 97/11080 {preferably A-119435, of which the chemical name is17-ethyl-1,14-dihydroxy-12-[2-[4-(acetylaminoacetylthio)-3-methoxycyclohexyl]-1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0^(4,9)]octacos-18-ene-2,3,10,16-tetrone.},and

17-ethyl-1,14-dihydroxy-12-[2-[4-(2-phenylhydrazinocarbonyloxy)-3-methoxycyclohexyl]-1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0^(4,9)]octacos-18-ene-2,3,10,16-tetronedisclosed in Bioorg. Med. Chem. Lett., vol. 9 (2), 227–232 (1999).

The planar chemical structures of the typical compounds are shown below.

(2) Agents which have the action of inhibiting nucleoside synthesis inimmune cells, depress lymphocytic proliferation by inhibiting nucleosidesynthesis in the immune cells and show nonspecific immunosuppressiveactivity. Such agents, which have the action of inhibiting nucleosidesynthesis in the immune cells, include, for example,

a compound having the chemical structure disclosed in claim 1 of U.S.Pat. No. 3,888,843 (mizoribine, of which the chemical name is5-hydroxy-1-β-D-ribofuranosyl-1H-imidazole-4-carboxamide),

a compound having the general formula disclosed in claim 7 of U.S. Pat.No. 3,056,785 or a pharmacologically acceptable salt thereof [preferablyazathioprine, of which the chemical name is6-[(1-methyl-4-nitro-1H-imidazol-5-yl)thio]-1H-purine, and in thepresent invention azathioprine includes a pharmacologically acceptablesalt (hydrochloride) thereof],

a compound having the general formula (A) or a pharmacologicallyacceptable salt thereof disclosed in the specification of E.P.Publication Number 281,713 (U.S. Pat. No. 4,753,935) [preferablymycophenolate Mofetil, of which the chemical name is2-(4-morpholinyl)ethyl6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-(4E)-hexenoate.],

a compound having the general formula (I) or a pharmacologicallyacceptable salt thereof disclosed in the specification of E.P.Publication Number 13376 (Japanese Patent Publication (Kokai) Number Sho62-72614 or U.S. Pat. No. 4,284,786) [preferably leflunomide, of whichthe chemical name is5-methyl-N-[4-(trifluoromethyl)phenyl]-4-isoxazolecarboxamide.],

a compound having the general formula (I) or a pharmacologicallyacceptable salt thereof disclosed in the specification of WO PublicationNumber 97/40028 {preferably merimempodib, of which the chemical name is(3s)-tetrahydro-3-furanyl[[3-[[[[3-methoxy-4-(5-oxazolyl)phenyl]amino]carbonyl]amino]phenyl]methyl]carbamate.},

a compound having the general formula (I) or a pharmacologicallyacceptable salt thereof disclosed in the specification of FR PatentPublication Number 2,727,628 [preferably HMR-1279, of which the chemicalname is α-cyano-N-(4-cyanophenyl)-β-oxo-cyclopropanepropaneamide.],

a compound having the general formula (I) or a pharmacologicallyacceptable salt thereof disclosed in the specification of WO PublicationNumber 93/22286 (Japanese Patent Number 2,928,385, E.P. PublicationNumber 601,191 or U.S. Pat. No. 5,371,225) {preferably TSK-204, of whichthe chemical name is6,7-dihydro-10-fluoro-3-(2-fluorophenyl)-5H-benzo[6,7]cyclohepta[1,2-b]quinoline-8-carboxylicacid.}, and

a compound having the general formula (I) or a pharmacologicallyacceptable salt thereof disclosed in the specification of E.P.Publication Number 569,912 (Japanese Patent Publication (Kokai) NumberHei 6-32784) {preferably SP-100030, of which the chemical name is2-chloro-N-[3,5-di(trifluoromethyl)phenyl]-4-(trifluoromethyl)pyrimidine-5-carboxyamide.}.

The planar chemical structures of the typical compounds are shown below.

(3) Agents which inhibit the action of cytokines on immune cells andhave antirheumatic action, have the combination of suppression ofcytokine production, suppression of lymphocytic proliferation, andsuppression of immunoglobulin production. Furthermore, the agentsinclude compounds having suppressive action on T-cell proliferation,suppression of NK cell activity, TNF-receptor antagonistic action, andthe like. Such agents, which inhibit the action of cytokine on immunecells and have antirheumatic action, include, for example,

a compound having the general formula disclosed in claim (1) of JapanesePatent Publication (Kokai) Number Hei 2-49778 or a pharmacologicallyacceptable salt thereof (preferably T-614, of which the chemical name isN-[3-formylamino-4-oxo-6-phenoxy-4H-1-benzopyran-7-yl]methanesulfonamide.),

a compound having the general formula (I) disclosed in the specificationof U.S. Pat. No. 4,720,506 or a pharmacologically acceptable saltthereof [preferably actarit, of which the chemical name is4-(acetylamino)phenylacetic acid.],

a compound having the general formula disclosed in claim 1 of U.S. Pat.No. 2,396,145 or a pharmacologically acceptable salt thereof {preferablysalazosulfapyridine, of which the chemical name is5-[[p-(2-pyridylsulfamoyl)-phenyl]azo]salicylic acid.}, and

a compound having the general formula (I) disclosed in the specificationof WO Publication Number 97/23457 {preferably CDC-801, of which thechemical name is3-phthalimido-3-(3-cyclopentyloxy-4-methoxyphenyl)propionamide.}.

The planar chemical structures of the typical compounds are shown below.

(4) Agents which are alkylating agents causing cell death by breakdownof DNA chains or blocking DNA synthesis, include, for example,

a compound having the general formula (IIIa) or a pharmacologicallyacceptable salt thereof disclosed in the specification of U.S. Pat. No.3,018,302 [preferably cyclophosphamide, of which the chemical name isN,N′-bis-(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine2-oxide.].

(5) Metabolic antagonists, which inhibit the metabolism of nucleic acidsby blocking folic acid production, have the action of inhibiting themetabolism of nucleic acids by binding to dihydrofolate reductases andblocking the production of tetrahydrofolic acids that are essential tothe synthesis of components of nucleic acids. Such metabolicantagonists, which inhibit the metabolism of nucleic acids by blockingfolic acid production, include, for example,

a compound having the general formula disclosed in claim 1 of U.S. Pat.No. 2,512,572 or a pharmacologically acceptable salt thereof {preferablymethotrexate, of which the chemical name isN-[4-[[2,4-diamino-6-pteridinyl]methyl]methylamino]benzoyl-1-glutamicacid}.

(6) The group of protein drugs, which have the suppression action ofTNF-alpha, includes compounds such as IL-1 receptor antagonists, solubleIL-1 receptors, and anti-IL-6 receptor antibodies, which suppress theaction of TNF-alpha by inhibiting the neutralizing action of circulatingTNF-alpha and its receptor-mediated intracellular TNF-alpha signaling.Such protein drugs, which have the inhibitory action of TNF-alpha,include, for example,

remicade (infliximab) disclosed in the specification of U.S. Pat. No.5,656,272 and Drugs, vol. 59(6), 1341–1359 (2000),

enbrel (etanercept) disclosed in the specification of WO PublicationNumber 94/06,476, U.S. Pat. No. 5,605,690, and Expert. Opin.Pharmacother., July vol. 2(7), 1137–1148 (2000),

daclizumab disclosed in the specification of WO Publication Number92/11,018, U.S. Pat. No. 5,530,101, and N. Engl. J. Med., vol. 338(3),161–165 (1997),

basiliximab disclosed in the specification of E.P. Publication Number449,769 and Clin. Pharmacol. Ther., Vol. 64(1), 66–72 (1998),

alemtuzumab disclosed in the specification of WO Publication Number89/07,452, U.S. Pat. No. 5,846,534, and J. Clin. Oncol., vol. 15(4),1567–1574 (1997),

omalizumab disclosed in the specification of U.S. Pat. No. 5,965,709 andDrugs vol. 61(2), 253–260 (2001),

BMS-188667 disclosed in the specification of E.P. Publication Number613,944 and J. Pharm. Sci., vol. 84(12), 1488–1489 (1995),

CDP-571 disclosed in Arthritis-Rheum., vol. 37(9), Suppl., S295 (1994),

inolimomab and ATM-027 disclosed in Transplant., June, vol. 55,1320–1327 (1993), and

BTI-322 disclosed in Blood, December 1, vol. 92(11), 4066–4071 (1998).

(7) Agents which are steroid hormone agents that bind to intracellularsteroid receptors to form a complex which binds to reaction sites onchromosomes, resulting in the synthesis of proteins which showimmunosuppressive activity, include, for example, prednisolone (of whichthe chemical name is 1,4-pregnadiene-3,20-dione-11β,17α-21-triol.).

(8) Agents which are substances suppressing prostaglandin productionand/or nonsteroidal anti-inflammatory drugs antagonizing the action ofprostaglandin, include, for example,

a compound having the general formula disclosed in claim 1 of JapanesePatent Publication (Kokoku) Number Sho 58-4699 or a pharmacologicallyacceptable salt thereof {preferably loxoprofen sodium, of which thechemical name is sodium2-[4-(2-oxocyclopentan-1-ylmethyl)phenyl]propionate.},

a compound having the general formula I(A) or a pharmacologicallyacceptable salt thereof disclosed in the specification of U.S. Pat. No.3,558,690 {preferably diclofenac sodium, of which the chemical name issodium [o-(2,6-dichloroanilino)phenyl]acetate.},

a compound having the general formula (I) or a pharmacologicallyacceptable salt thereof disclosed in the specification of U.S. Pat. No.4,233,299 (E.P. Publication Number 0,002,482 or Japanese PatentPublication (Kokai) Number Sho 58-92976) [preferably meloxicam, of whichthe chemical name is4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide1,1-dioxide.],

a compound having the general formula (II) or a pharmacologicallyacceptable salt thereof disclosed in the specification of WO PublicationNumber 95/15316 (U.S. Pat. No. 5,521,207 or Japanese Patent Publication(Kokai) Number 2000-109466) {preferably celecoxib, of which the chemicalname is4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide.},and

a compound having the general formula (I) or a pharmacologicallyacceptable salt thereof disclosed in the specification of WO PublicationNumber 95/00501 (U.S. Pat. No. 5,474,995) {preferably rofecoxib, ofwhich the chemical name is4-[4-(methylsulfonyl)phenyl]-3-phenyl-2(5H)-furanone.}.

Of the above immunosuppressants, more preferred are cyclosporin A,tacrolimus, rapamycin, leflunomide, methotrexate, remicade and enbrel.

The “pharmacologically acceptable salt thereof” described above means asalt into which the above immunosuppressants can be converted, byreacting a compound having a basic group such as an amino group with anacid or by reacting a compound having an acidic group such as a carboxylgroup with a base. Such salts are included in the present invention.

The salt formed with a basic group of the above immunosuppressants ispreferably an inorganic acid salt, for example, a hydrohalide such ashydrofluoride, hydrochloride, hydrobromide, or hydroiodide, a nitrate, aperchlorate, a sulfate, a phosphate or the like; an organic acid salt,for example, a lower alkanesulfonate such as methanesulfonate,trifluoromethanesulfonate, or ethanesulfonate, an arylsulfonate such asbenzenesulfonate or p-toluenesulfonate, an acetate, a malate, afumarate, a succinate, a citrate, an ascorbate, a tartrate, a oxalate, amaleate, or the like; or an amino acid salt such as glycine salt, lysinesalt, arginine salt, ornithine salt, glutamate, or aspartic acid salt.The salt is more preferably hydrochloride, acetate, fumarate, succinate,or maleate.

The salt formed with an acidic group of the above immunosuppressants ispreferably a metal salt, for example, an alkali metal salt such assodium salt, potassium salt, or lithium salt, an alkaline earth metalsalt such as calcium salt or magnesium salt, an aluminum salt, an ironsalt, or the like; an amine salt, for example, an inorganic salt such asammonium salt, an organic acid salt such as t-octylamine salt,dibenzylamine salt, morpholine salt, glucosamine salt, phenylglycinealkyl ester salt, ethylenediamine salt, N-methylglucamine salt,guanidine salt, diethylamine salt, triethylamine salt, dicyclohexylaminesalt, N,N′-dibenzylethylenediamine salt, chloroprocaine salt, procainesalt, diethanolamine salt, N-benzylphenethylamine salt, piperazine salt,tetramethylammonium salt, tris(hydroxymethyl)aminomethane salt, or thelike; or an amino acid salt such as glycine salt, lysine salt, argininesalt, ornithine salt, glutamic acid salt, or aspartic acid salt. Thesalt is more preferably sodium salt, potassium salt, calcium salt,magnesium salt, or aluminum salt.

When the immunosuppressants, the active ingredients of thepharmaceutical compositions of the present invention, are allowed tostand in contact with the atmosphere or to recrystallize, they mayabsorb water or water may attach to them to form a hydrate. The presentinvention encompasses such hydrates.

When the immunosuppressants, the active ingredients of thepharmaceutical compositions of the present invention, have asymmetriccarbons in their structures, these compounds can exist as variousstereoisomers due to such asymmetric carbons. In the present inventionthese compounds are represented as a single chemical formulaindividually. The present invention encompasses both individualstereoisomers and mixtures of two or more stereoisomers in any ratio.

Compounds shown in the following Table 1, Table 2, Table 3, Table 4,Table 5 and Table 6 are specifically illustrated as preferred compoundsof general formula (I), (II), or (III) of the present invention.However, the compounds of the present invention are not limited tothese.

The compounds represented by the same compound number in Table 1 andTable 2 include compounds wherein X is a sulfur atom (S), an oxygen atom(O), or a group of formula ═N—CH₃.

The compounds represented by the same compound number in Table 5 andTable 6 include the six types of compounds wherein X is a sulfur atom(S), an oxygen atom (O), or a group of formula ═N—CH₃, and the phosphategroup is linked to an oxygen atom (O) or a —CH₂— group.

The meaning of the abbreviations in the following Tables is shown below.

-   Bu represents a butyl group,-   iBu represents a isobutyl group,-   Bz represents a benzyl group,-   Et represents an ethyl group,-   cHx represents a cyclohexyl group,-   Me represents a methyl group,-   Np(1) represents a naphthalen-1-yl group,-   Np(2) represents a naphthalen-2-yl group,-   Ph represents a phenyl group,-   cPn represents a cyclopentyl group,-   Pr represents a propyl group, and-   iPr represents an isopropyl group.

TABLE 1

or

Compd. R¹ R² R³ R⁴ n —Y—Z—R⁵ R⁶ R⁷ 1-1 H H H Me 2 —(CH₂)₃-cHx H H 1-2 HH H Me 2 —(CH₂)₃-(4-F-cHx) H H 1-3 H H H Me 2 —(CH₂)₃-(4-Me-cHx) H H 1-4H H H Me 2 —(CH₂)₃-(4-Et-cHx) H H 1-5 H H H Me 2 —(CH₂)₃-(4-CF₃-cHx) H H1-6 H H H Me 2 —(CH₂)₃-(4-MeO-cHx) H H 1-7 H H H Me 2—(CH₂)₃-(4-EtO-cHx) H H 1-8 H H H Me 2 —(CH₂)₃-(4-MeS-cHx) H H 1-9 H H HMe 2 —(CH₂)₃-(4-cHx-cHx) H H 1-10 H H H Me 2 —(CH₂)₃-(4-Ph-cHx) H H 1-11H H H Me 2 —(CH₂)₃-Ph H H 1-12 H H H Me 2 —(CH₂)₃-(4-F-Ph) H H 1-13 H HH Me 2 —(CH₂)₃-(4-Me-Ph) H H 1-14 H H H Me 2 —(CH₂)₃-(4-Et-Ph) H H 1-15H H H Me 2 —(CH₂)₃-(4-CF₃-Ph) H H 1-16 H H H Me 2 —(CH₂)₃-(4-MeO-Ph) H H1-17 H H H Me 2 —(CH₂)₃-(4-EtO-Ph) H H 1-18 H H H Me 2—(CH₂)₃-(4-MeS-Ph) H H 1-19 H H H Me 2 —(CH₂)₃-(4-cHx-Ph) H H 1-20 H H HMe 2 —(CH₂)₃-(4-Ph-Ph) H H 1-21 H H H Me 2 —(CH₂)₄-cHx H H 1-22 H H H Me2 —(CH₂)₄-(4-F-cHx) H H 1-23 H H H Me 2 —(CH₂)₄-(4-Me-cHx) H H 1-24 H HH Me 2 —(CH₂)₄-(4-Et-cHx) H H 1-25 H H H Me 2 —(CH₂)₄-(4-CF₃-cHx) H H1-26 H H H Me 2 —(CH₂)₄-(4-MeO-cHx) H H 1-27 H H H Me 2—(CH₂)₄-(4-EtO-cHx) H H 1-28 H H H Me 2 —(CH₂)₄-(4-MeS-cHx) H H 1-29 H HH Me 2 —(CH₂)₄-(4-cHx-cHx) H H 1-30 H H H Me 2 —(CH₂)₄-(4-Ph-cHx) H H1-31 H H H Me 2 —(CH₂)₄-Ph H H 1-32 H H H Me 2 —(CH₂)₄-(4-F-Ph) H H 1-33H H H Me 2 —(CH₂)₄-(4-Me-Ph) H H 1-34 H H H Me 2 —(CH₂)₄-(4-Et-Ph) H H1-35 H H H Me 2 —(CH₂)₄-(4-CF₃-Ph) H H 1-36 H H H Me 2—(CH₂)₄-(4-MeO-Ph) H H 1-37 H H H Me 2 —(CH₂)₄-(4-EtO-Ph) H H 1-38 H H HMe 2 —(CH₂)₄-(4-MeS-Ph) H H 1-39 H H H Me 2 —(CH₂)₄-(4-cHx-Ph) H H 1-40H H H Me 2 —(CH₂)₄-(4-Ph-Ph) H H 1-41 H H H Me 2 —(CH₂)₅-cPn H H 1-42 HH H Me 2 —(CH₂)₅-cHx H H 1-43 H H H Me 2 —(CH₂)₅-cHx Me H 1-44 H H H Me2 —(CH₂)₅-cHx H Me 1-45 H H H Me 2 —(CH₂)₅-cHx F H 1-46 H H H Me 2—(CH₂)₅-cHx H F 1-47 H H H Me 2 —(CH₂)₅-(3-F-cHx) H H 1-48 H H H Me 2—(CH₂)₅-(4-F-cHx) H H 1-49 H H H Me 2 —(CH₂)₅-(4-Cl-cHx) H H 1-50 H H HMe 2 —(CH₂)₅-(4-Br-cHx) H H 1-51 H H H Me 2 —(CH₂)₅-(3-Me-cHx) H H 1-52H H H Me 2 —(CH₂)₅-(4-Me-cHx) H H 1-53 H H H Me 2 —(CH₂)₅-(3-Et-cHx) H H1-54 H H H Me 2 —(CH₂)₅-(4-Et-cHx) H H 1-55 H H H Me 2—(CH₂)₅-(3-Pr-cHx) H H 1-56 H H H Me 2 —(CH₂)₅-(4-Pr-cHx) H H 1-57 H H HMe 2 —(CH₂)₅-(4-iPr-cHx) H H 1-58 H H H Me 2 —(CH₂)₅-(3-Bu-cHx) H H 1-59H H H Me 2 —(CH₂)₅-(4-Bu-cHx) H H 1-60 H H H Me 2 —(CH₂)₅-(3-CF₃-cHx) HH 1-61 H H H Me 2 —(CH₂)₅-(4-CF₃-cHx) H H 1-62 H H H Me 2—(CH₂)₅-(3-MeO-cHx) H H 1-63 H H H Me 2 —(CH₂)₅-(4-MeO-cHx) H H 1-64 H HH Me 2 —(CH₂)₅-(3-EtO-cHx) H H 1-65 H H H Me 2 —(CH₂)₅-(4-EtO-cHx) H H1-66 H H H Me 2 —(CH₂)₅-(3-PrO-cHx) H H 1-67 H H H Me 2—(CH₂)₅-(4-PrO-cHx) H H 1-68 H H H Me 2 —(CH₂)₅-(3-iPrO-cHx) H H 1-69 HH H Me 2 —(CH₂)₅-(4-iPrO-cHx) H H 1-70 H H H Me 2—(CH₂)₅-[3-(2-Et-PrO)-cHx] H H 1-71 H H H Me 2—(CH₂)₅-[4-(2-Et-PrO)-cHx] H H 1-72 H H H Me 2 —(CH₂)₅-(3-iBuO-cHx) H H1-73 H H H Me 2 —(CH₂)₅-(4-iBuO-cHx) H H 1-74 H H H Me 2—(CH₂)₅-(3-MeS-cHx) H H 1-75 H H H Me 2 —(CH₂)₅-(4-MeS-cHx) H H 1-76 H HH Me 2 —(CH₂)₅-(3-EtS-cHx) H H 1-77 H H H Me 2 —(CH₂)₅-(4-EtS-cHx) H H1-78 H H H Me 2 —(CH₂)₅-(3-PrS-cHx) H H 1-79 H H H Me 2—(CH₂)₅-(4-PrS-cHx) H H 1-80 H H H Me 2 —(CH₂)₅-(3-iPrS-cHx) H H 1-81 HH H Me 2 —(CH₂)₅-(4-iPrS-cHx) H H 1-82 H H H Me 2—(CH₂)₅-[3-(2-Et-PrS)-cHx] H H 1-83 H H H Me 2—(CH₂)₅-[4-(2-Et-PrS)-cHx] H H 1-84 H H H Me 2 —(CH₂)₅-(3-iBuS-cHx) H H1-85 H H H Me 2 —(CH₂)₅-(4-iBuS-cHx) H H 1-86 H H H Me 2—(CH₂)₅-(3-cHx-cHx) H H 1-87 H H H Me 2 —(CH₂)₅-(4-cHx-cHx) H H 1-88 H HH Me 2 —(CH₂)₅-(3-Ph-cHx) H H 1-89 H H H Me 2 —(CH₂)₅-(4-Ph-cHx) H H1-90 H H H Me 2 —(CH₂)₅-(2,4-diMe-cHx) H H 1-91 H H H Me 2—(CH₂)₅-(3,4-diMe-cHx) H H 1-92 H H H Me 2 —(CH₂)₅-(3,5-diMe-cHx) H H1-93 H H H Me 2 —(CH₂)₅-Ph H H 1-94 H H H Me 2 —(CH₂)₅-Ph Me H 1-95 H HH Me 2 —(CH₂)₅-Ph H Me 1-96 H H H Me 2 —(CH₂)₅-Ph F H 1-97 H H H Me 2—(CH₂)₅-Ph H F 1-98 H H H Me 2 —(CH₂)₅-(3-F-Ph) H H 1-99 H H H Me 2—(CH₂)₅-(4-F-Ph) H H 1-100 H H H Me 2 —(CH₂)₅-(4-Cl-Ph) H H 1-101 H H HMe 2 —(CH₂)₅-(4-Br-Ph) H H 1-102 H H H Me 2 —(CH₂)₅-(3-Me-Ph) H H 1-103H H H Me 2 —(CH₂)₅-(4-Me-Ph) H H 1-104 H H H Me 2 —(CH₂)₅-(3-Et-Ph) H H1-105 H H H Me 2 —(CH₂)₅-(4-Et-Ph) H H 1-106 H H H Me 2—(CH₂)₅-(3-Pr-Ph) H H 1-107 H H H Me 2 —(CH₂)₅-(4-Pr-Ph) H H 1-108 H H HMe 2 —(CH₂)₅-(3-iPr-Ph) H H 1-109 H H H Me 2 —(CH₂)₅-(4-iPr-Ph) H H1-110 H H H Me 2 —(CH₂)₅-(3-Bu-Ph) H H 1-111 H H H Me 2—(CH₂)₅-(4-Bu-Ph) H H 1-112 H H H Me 2 —(CH₂)₅-(3-CF₃-Ph) H H 1-113 H HH Me 2 —(CH₂)₅-(4-CF₃-Ph) H H 1-114 H H H Me 2 —(CH₂)₅-(3-MeO-Ph) H H1-115 H H H Me 2 —(CH₂)₅-(4-MeO-Ph) H H 1-116 H H H Me 2—(CH₂)₅-(3-EtO-Ph) H H 1-117 H H H Me 2 —(CH₂)₅-(4-EtO-Ph) H H 1-118 H HH Me 2 —(CH₂)₅-(3-PrO-Ph) H H 1-119 H H H Me 2 —(CH₂)₅-(4-PrO-Ph) H H1-120 H H H Me 2 —(CH₂)₅-(3-iPrO-Ph) H H 1-121 H H H Me 2—(CH₂)₅-(4-iPrO-Ph) H H 1-122 H H H Me 2 —(CH₂)₅-[3-(2-Et-PrO)-Ph] H H1-123 H H H Me 2 —(CH₂)₅-[4-(2-Et-PrO)-Ph] H H 1-124 H H H Me 2—(CH₂)₅-(3-iBuO-Ph) H H 1-125 H H H Me 2 —(CH₂)₅-(4-iBuO-Ph) H H 1-126 HH H Me 2 —(CH₂)₅-(3-MeS-Ph) H H 1-127 H H H Me 2 —(CH₂)₅-(4-MeS-Ph) H H1-128 H H H Me 2 —(CH₂)₅-(3-EtS-Ph) H H 1-129 H H H Me 2—(CH₂)₅-(4-EtS-Ph) H H 1-130 H H H Me 2 —(CH₂)₅-(3-PrS-Ph) H H 1-131 H HH Me 2 —(CH₂)₅-(4-PrS-Ph) H H 1-132 H H H Me 2 —(CH₂)₅-(3-iPrS-Ph) H H1-133 H H H Me 2 —(CH₂)₅-(4-iPrS-Ph) H H 1-134 H H H Me 2—(CH₂)₅-[3-(2-Et-PrS)-Ph] H H 1-135 H H H Me 2 —(CH₂)₅-[4-(2-Et-PrS)-Ph]H H 1-136 H H H Me 2 —(CH₂)₅-(3-iBuS-Ph) H H 1-137 H H H Me 2—(CH₂)₅-(4-iBuS-Ph) H H 1-138 H H H Me 2 —(CH₂)₅-(3-cHx-Ph) H H 1-139 HH H Me 2 —(CH₂)₅-(4-cHx-Ph) H H 1-140 H H H Me 2 —(CH₂)₅-(3-Ph-Ph) H H1-141 H H H Me 2 —(CH₂)₅-(4-Ph-Ph) H H 1-142 H H H Me 2—(CH₂)₅-(2,4-diMe-Ph) H H 1-143 H H H Me 2 —(CH₂)₅-(3,4-diMe-Ph) H H1-144 H H H Me 2 —(CH₂)₅-(3,5-diMe-Ph) H H 1-145 H H H Me 2—(CH₂)₅-Np(1) H H 1-146 H H H Me 2 —(CH₂)₅-Np(2) H H 1-147 H H H Me 2—(CH₂)₆-cPn H H 1-148 H H H Me 2 —(CH₂)₆-cHx H H 1-149 H H H Me 2—(CH₂)₆-cHx Me H 1-150 H H H Me 2 —(CH₂)₆-cHx H Me 1-151 H H H Me 2—(CH₂)₆-cHx F H 1-152 H H H Me 2 —(CH₂)₆-cHx H F 1-153 H H H Me 2—(CH₂)₆-(3-F-cHx) H H 1-154 H H H Me 2 —(CH₂)₆-(4-F-cHx) H H 1-155 H H HMe 2 —(CH₂)₆-(4-Cl-cHx) H H 1-156 H H H Me 2 —(CH₂)₆-(4-Br-cHx) H H1-157 H H H Me 2 —(CH₂)₆-(3-Me-cHx) H H 1-158 H H H Me 2—(CH₂)₆-(4-Me-cHx) H H 1-159 H H H Me 2 —(CH₂)₆-(3-Et-cHx) H H 1-160 H HH Me 2 —(CH₂)₆-(4-Et-cHx) H H 1-161 H H H Me 2 —(CH₂)₆-(3-Pr-cHx) H H1-162 H H H Me 2 —(CH₂)₆-(4-Pr-cHx) H H 1-163 H H H Me 2—(CH₂)₆-(4-iPr-cHx) H H 1-164 H H H Me 2 —(CH₂)₆-(3-Bu-cHx) H H 1-165 HH H Me 2 —(CH₂)₆-(4-Bu-cHx) H H 1-166 H H H Me 2 —(CH₂)₆-(3-CF₃-cHx) H H1-167 H H H Me 2 —(CH₂)₆-(4-CF₃-cHx) H H 1-168 H H H Me 2—(CH₂)₆-(3-MeO-cHx) H H 1-169 H H H Me 2 —(CH₂)₆-(4-MeO-cHx) H H 1-170 HH H Me 2 —(CH₂)₆-(3-EtO-cHx) H H 1-171 H H H Me 2 —(CH₂)₆-(4-EtO-cHx) HH 1-172 H H H Me 2 —(CH₂)₆-(3-PrO-cHx) H H 1-173 H H H Me 2—(CH₂)₆-(4-PrO-cHx) H H 1-174 H H H Me 2 —(CH₂)₆-(3-iPrO-cHx) H H 1-175H H H Me 2 —(CH₂)₆-(4-iPrO-cHx) H H 1-176 H H H Me 2—(CH₂)₆-[3-(2-Et-PrO)-cHx] H H 1-177 H H H Me 2—(CH₂)₆-[4-(2-Et-PrO)-cHx] H H 1-178 H H H Me 2 —(CH₂)₆-(3-iBuO-cHx) H H1-179 H H H Me 2 —(CH₂)₆-(4-iBuO-cHx) H H 1-180 H H H Me 2—(CH₂)₆-(3-MeS-cHx) H H 1-181 H H H Me 2 —(CH₂)₆-(4-MeS-cHx) H H 1-182 HH H Me 2 —(CH₂)₆-(3-EtS-cHx) H H 1-183 H H H Me 2 —(CH₂)₆-(4-EtS-cHx) HH 1-184 H H H Me 2 —(CH₂)₆-(3-PrS-cHx) H H 1-185 H H H Me 2—(CH₂)₆-(4-PrS-cHx) H H 1-186 H H H Me 2 —(CH₂)₆-(3-iPrS-cHx) H H 1-187H H H Me 2 —(CH₂)₆-(4-iPrS-cHx) H H 1-188 H H H Me 2—(CH₂)₆-[3-(2-Et-PrS)-cHx] H H 1-189 H H H Me 2—(CH₂)₆-(4-(2-Et-PrS)-cHx] H H 1-190 H H H Me 2 —(CH₂)₆-(3-iBuS-cHx) H H1-191 H H H Me 2 —(CH₂)₆-(4-iBuS-cHx) H H 1-192 H H H Me 2—(CH₂)₆-(3-cHx-cHx) H H 1-193 H H H Me 2 —(CH₂)₆-(4-cHx-cHx) H H 1-194 HH H Me 2 —(CH₂)₆-(3-Ph-cHx) H H 1-195 H H H Me 2 —(CH₂)₆-(4-Ph-cHx) H H1-196 H H H Me 2 —(CH₂)₆-(2,4-diMe-cHx) H H 1-197 H H H Me 2—(CH₂)₆-(3,4-diMe-cHx) H H 1-198 H H H Me 2 —(CH₂)₆-(3,5-diMe-cHx) H H1-199 H H H Me 2 —(CH₂)₆-Ph H H 1-200 H H H Me 2 —(CH₂)₆-Ph Me H 1-201 HH H Me 2 —(CH₂)₆-Ph H Me 1-202 H H H Me 2 —(CH₂)₆-Ph F H 1-203 H H H Me2 —(CH₂)₆-Ph H F 1-204 H H H Me 2 —(CH₂)₆-(3-F-Ph) H H 1-205 H H H Me 2—(CH₂)₆-(4-F-Ph) H H 1-206 H H H Me 2 —(CH₂)₆-(4-Cl-Ph) H H 1-207 H H HMe 2 —(CH₂)₆-(4-Br-Ph) H H 1-208 H H H Me 2 —(CH₂)₆-(3-Me-Ph) H H 1-209H H H Me 2 —(CH₂)₆-(4-Me-Ph) H H 1-210 H H H Me 2 —(CH₂)₆-(3-Et-Ph) H H1-211 H H H Me 2 —(CH₂)₆-(4-Et-Ph) H H 1-212 H H H Me 2—(CH₂)₆-(3-Pr-Ph) H H 1-213 H H H Me 2 —(CH₂)₆-(4-Pr-Ph) H H 1-214 H H HMe 2 —(CH₂)₆-(3-iPr-Ph) H H 1-215 H H H Me 2 —(CH₂)₆-(4-iPr-Ph) H H1-216 H H H Me 2 —(CH₂)₆-(3-Bu-Ph) H H 1-217 H H H Me 2—(CH₂)₆-(4-Bu-Ph) H H 1-218 H H H Me 2 —(CH₂)₆-(3-CF₃-Ph) H H 1-219 H HH Me 2 —(CH₂)₆-(4-CF₃-Ph) H H 1-220 H H H Me 2 —(CH₂)₆-(3-MeO-Ph) H H1-221 H H H Me 2 —(CH₂)₆-(4-MeO-Ph) H H 1-222 H H H Me 2—(CH₂)₆-(3-EtO-Ph) H H 1-223 H H H Me 2 —(CH₂)₆-(4-EtO-Ph) H H 1-224 H HH Me 2 —(CH₂)₆-(3-PrO-Ph) H H 1-225 H H H Me 2 —(CH₂)₆-(4-PrO-Ph) H H1-226 H H H Me 2 —(CH₂)₆-(3-iPrO-Ph) H H 1-227 H H H Me 2—(CH₂)₆-(4-iPrO-Ph) H H 1-228 H H H Me 2 —(CH₂)₆-[3-(2-Et-PrO)-Ph] H H1-229 H H H Me 2 —(CH₂)₆-[4-(2-Et-PrO)-Ph] H H 1-230 H H H Me 2—(CH₂)₆-(3-iBuO-Ph) H H 1-231 H H H Me 2 —(CH₂)₆-(4-iBuO-Ph) H H 1-232 HH H Me 2 —(CH₂)₆-(3-MeS-Ph) H H 1-233 H H H Me 2 —(CH₂)₆-(4-MeS-Ph) H H1-234 H H H Me 2 —(CH₂)₆-(3-EtS-Ph) H H 1-235 H H H Me 2—(CH₂)₆-(4-EtS-Ph) H H 1-236 H H H Me 2 —(CH₂)₆-(3-PrS-Ph) H H 1-237 H HH Me 2 —(CH₂)₆-(4-PrS-Ph) H H 1-238 H H H Me 2 —(CH₂)₆-(3-iPrS-Ph) H H1-239 H H H Me 2 —(CH₂)₆-(4-iPrS-Ph) H H 1-240 H H H Me 2—(CH₂)₆-[3-(2-Et-PrS)-Ph] H H 1-241 H H H Me 2 —(CH₂)₆-[4-(2-Et-PrS)-Ph]H H 1-242 H H H Me 2 —(CH₂)₆-(3-iBuS-Ph) H H 1-243 H H H Me 2—(CH₂)₆-(4-iBuS-Ph) H H 1-244 H H H Me 2 —(CH₂)₆-(3-cHx-Ph) H H 1-245 HH H Me 2 —(CH₂)₆-(4-cHx-Ph) H H 1-246 H H H Me 2 —(CH₂)₆-(3-Ph-Ph) H H1-247 H H H Me 2 —(CH₂)₆-(4-Ph-Ph) H H 1-248 H H H Me 2—(CH₂)₆-(2,4-diMe-Ph) H H 1-249 H H H Me 2 —(CH₂)₆-(3,4-diMe-Ph) H H1-250 H H H Me 2 —(CH₂)₆-(3,5-diMe-Ph) H H 1-251 H H H Me 2—(CH₂)₆-Np(1) H H 1-252 H H H Me 2 —(CH₂)₆-Np(2) H H 1-253 H H H Me 2—(CH₂)₇-cHx H H 1-254 H H H Me 2 —(CH₂)₇-(4-F-cHx) H H 1-255 H H H Me 2—(CH₂)₇-(4-Me-cHx) H H 1-256 H H H Me 2 —(CH₂)₇-(4-Et-cHx) H H 1-257 H HH Me 2 —(CH₂)₇-(4-CF₃-cHx) H H 1-258 H H H Me 2 —(CH₂)₇-(4-MeO-cHx) H H1-259 H H H Me 2 —(CH₂)₇-(4-EtO-cHx) H H 1-260 H H H Me 2—(CH₂)₇-(4-MeS-cHx) H H 1-261 H H H Me 2 —(CH₂)₇-(4-cHx-cHx) H H 1-262 HH H Me 2 —(CH₂)₇-(4-Ph-cHx) H H 1-263 H H H Me 2 —(CH₂)₇-Ph H H 1-264 HH H Me 2 —(CH₂)₇-(4-F-Ph) H H 1-265 H H H Me 2 —(CH₂)₇-(4-Me-Ph) H H1-266 H H H Me 2 —(CH₂)₇-(4-Et-Ph) H H 1-267 H H H Me 2—(CH₂)₇-(4-CF₃-Ph) H H 1-268 H H H Me 2 —(CH₂)₇-(4-MeO-Ph) H H 1-269 H HH Me 2 —(CH₂)₇-(4-EtO-Ph) H H 1-270 H H H Me 2 —(CH₂)₇-(4-MeS-Ph) H H1-271 H H H Me 2 —(CH₂)₇-(4-cHx-Ph) H H 1-272 H H H Me 2—(CH₂)₇-(4-Ph-Ph) H H 1-273 H H H Me 2 —(CH₂)₃—O-cHx H H 1-274 H H H Me2 —(CH₂)₃—O-(4-F-cHx) H H 1-275 H H H Me 2 —(CH₂)₃—O-(4-Me-cHx) H H1-276 H H H Me 2 —(CH₂)₃—O-(4-Et-cHx) H H 1-277 H H H Me 2—(CH₂)₃—O-(4-CF₃-cHx) H H 1-278 H H H Me 2 —(CH₂)₃—O-(4-MeO-cHx) H H1-279 H H H Me 2 —(CH₂)₃—O-(4-EtO-cHx) H H 1-280 H H H Me 2—(CH₂)₃—O-(4-MeS-cHx) H H 1-281 H H H Me 2 —(CH₂)₃—O-(4-cHx-cHx) H H1-282 H H H Me 2 —(CH₂)₃—O-(4-Ph-cHx) H H 1-283 H H H Me 2 —(CH₂)₃—O-PhH H 1-284 H H H Me 2 —(CH₂)₃—O-(4-F-Ph) H H 1-285 H H H Me 2—(CH₂)₃—O-(4-Me-Ph) H H 1-286 H H H Me 2 —(CH₂)₃—O-(4-Et-Ph) H H 1-287 HH H Me 2 —(CH₂)₃—O-(4-CF₃-Ph) H H 1-288 H H H Me 2 —(CH₂)₃—O-(4-MeO-Ph)H H 1-289 H H H Me 2 —(CH₂)₃—O-(4-EtO-Ph) H H 1-290 H H H Me 2—(CH₂)₃—O-(4-MeS-Ph) H H 1-291 H H H Me 2 —(CH₂)₃—O-(4-cHx-Ph) H H 1-292H H H Me 2 —(CH₂)₃—O-(4-Ph-Ph) H H 1-293 H H H Me 2 —(CH₂)₄—O-cPn H H1-294 H H H Me 2 —(CH₂)₄—O-cHx H H 1-295 H H H Me 2 —(CH₂)₄—O-cHx Me H1-296 H H H Me 2 —(CH₂)₄—O-cHx H Me 1-297 H H H Me 2 —(CH₂)₄—O-cHx F H1-298 H H H Me 2 —(CH₂)₄—O-cHx H F 1-299 H H H Me 2 —(CH₂)₄—O-(3-F-cHx)H H 1-300 H H H Me 2 —(CH₂)₄—O-(4-F-cHx) H H 1-301 H H H Me 2—(CH₂)₄—O-(4-Cl-cHx) H H 1-302 H H H Me 2 —(CH₂)₄—O-(4-Br-cHx) H H 1-303H H H Me 2 —(CH₂)₄—O-(3-Me-cHx) H H 1-304 H H H Me 2—(CH₂)₄—O-(4-Me-cHx) H H 1-305 H H H Me 2 —(CH₂)₄—O-(3-Et-cHx) H H 1-306H H H Me 2 —(CH₂)₄—O-(4-Et-cHx) H H 1-307 H H H Me 2—(CH₂)₄—O-(3-Pr-cHx) H H 1-308 H H H Me 2 —(CH₂)₄—O-(4-Pr-cHx) H H 1-309H H H Me 2 —(CH₂)₄—O-(4-iPr-cHx) H H 1-310 H H H Me 2—(CH₂)₄—O-(3-Bu-cHx) H H 1-311 H H H Me 2 —(CH₂)₄—O-(4-Bu-cHx) H H 1-312H H H Me 2 —(CH₂)₄—O-(3-CF₃-cHx) H H 1-313 H H H Me 2—(CH₂)₄—O-(4-CF₃-cHx) H H 1-314 H H H Me 2 —(CH₂)₄—O-(3-MeO-cHx) H H1-315 H H H Me 2 —(CH₂)₄—O-(4-MeO-cHx) H H 1-316 H H H Me 2—(CH₂)₄—O-(3-EtO-cHx) H H 1-317 H H H Me 2 —(CH₂)₄—O-(4-EtO-cHx) H H1-318 H H H Me 2 —(CH₂)₄—O-(3-PrO-cHx) H H 1-319 H H H Me 2—(CH₂)₄—O-(4-PrO-cHx) H H 1-320 H H H Me 2 —(CH₂)₄—O-(3-iPrO-cHx) H H1-321 H H H Me 2 —(CH₂)₄—O-(4-iPrO-cHx) H H 1-322 H H H Me 2—(CH₂)₄—O-[3-(2-Et-PrO)-cHx] H H 1-323 H H H Me 2—(CH₂)₄—O-[4-(2-Et-PrO)-cHx] H H 1-324 H H H Me 2 —(CH₂)₄—O-(3-iBuO-cHx)H H 1-325 H H H Me 2 —(CH₂)₄—O-(4-iBuO-cHx) H H 1-326 H H H Me 2—(CH₂)₄—O-(3-MeS-cHx) H H 1-327 H H H Me 2 —(CH₂)₄—O-(4-MeS-cHx) H H1-328 H H H Me 2 —(CH₂)₄—O-(3-EtS-cHx) H H 1-329 H H H Me 2—(CH₂)₄—O-(4-EtS-cHx) H H 1-330 H H H Me 2 —(CH₂)₄—O-(3-PrS-cHx) H H1-331 H H H Me 2 —(CH₂)₄—O-(4-PrS-cHx) H H 1-332 H H H Me 2—(CH₂)₄—O-(3-iPrS-cHx) H H 1-333 H H H Me 2 —(CH₂)₄—O-(4-iPrS-cHx) H H1-334 H H H Me 2 —(CH₂)₄—O-[3-(2-Et-PrS)-cHx] H H 1-335 H H H Me 2—(CH₂)₄—O-[4-(2-Et-PrS)-cHx] H H 1-336 H H H Me 2 —(CH₂)₄—O-(3-iBuS-cHx)H H 1-337 H H H Me 2 —(CH₂)₄—O-(4-iBuS-cHx) H H 1-338 H H H Me 2—(CH₂)₄—O-(3-cHx-cHx) H H 1-339 H H H Me 2 —(CH₂)₄—O-(4-cHx-cHx) H H1-340 H H H Me 2 —(CH₂)₄—O-(3-Ph-cHx) H H 1-341 H H H Me 2—(CH₂)₄—O-(4-Ph-cHx) H H 1-342 H H H Me 2 —(CH₂)₄—O-(2,4-diMe-cHx) H H1-343 H H H Me 2 —(CH₂)₄—O-(3,4-diMe-cHx) H H 1-344 H H H Me 2—(CH₂)₄—O-(3,5-diMe-cHx) H H 1-345 H H H Me 2 —(CH₂)₄—O-Ph H H 1-346 H HH Me 2 —(CH₂)₄—O-Ph Me H 1-347 H H H Me 2 —(CH₂)₄—O-Ph H Me 1-348 H H HMe 2 —(CH₂)₄—O-Ph F H 1-349 H H H Me 2 —(CH₂)₄—O-Ph H F 1-350 H H H Me 2—(CH₂)₄—O-(3-F-Ph) H H 1-351 H H H Me 2 —(CH₂)₄—O-(4-F-Ph) H H 1-352 H HH Me 2 —(CH₂)₄—O-(4-Cl-Ph) H H 1-353 H H H Me 2 —(CH₂)₄—O-(4-Br-Ph) H H1-354 H H H Me 2 —(CH₂)₄—O-(3-Me-Ph) H H 1-355 H H H Me 2—(CH₂)₄—O-(4-Me-Ph) H H 1-356 H H H Me 2 —(CH₂)₄—O-(3-Et-Ph) H H 1-357 HH H Me 2 —(CH₂)₄—O-(4-Et-Ph) H H 1-358 H H H Me 2 —(CH₂)₄—O-(3-Pr-Ph) HH 1-359 H H H Me 2 —(CH₂)₄—O-(4-Pr-Ph) H H 1-360 H H H Me 2—(CH₂)₄—O-(3-iPr-Ph) H H 1-361 H H H Me 2 —(CH₂)₄—O-(4-iPr-Ph) H H 1-362H H H Me 2 —(CH₂)₄—O-(3-Bu-Ph) H H 1-363 H H H Me 2 —(CH₂)₄—O-(4-Bu-Ph)H H 1-364 H H H Me 2 —(CH₂)₄—O-(3-CF₃-Ph) H H 1-365 H H H Me 2—(CH₂)₄—O-(4-CF₃-Ph) H H 1-366 H H H Me 2 —(CH₂)₄—O-(3-MeO-Ph) H H 1-367H H H Me 2 —(CH₂)₄—O-(4-MeO-Ph) H H 1-368 H H H Me 2—(CH₂)₄—O-(3-EtO-Ph) H H 1-369 H H H Me 2 —(CH₂)₄—O-(4-EtO-Ph) H H 1-370H H H Me 2 —(CH₂)₄—O-(3-PrO-Ph) H H 1-371 H H H Me 2—(CH₂)₄—O-(4-PrO-Ph) H H 1-372 H H H Me 2 —(CH₂)₄—O-(3-iPrO-Ph) H H1-373 H H H Me 2 —(CH₂)₄—O-(4-iPrO-Ph) H H 1-374 H H H Me 2—(CH₂)₄—O-[3-(2-Et-PrO)-Ph] H H 1-375 H H H Me 2—(CH₂)₄—O-[4-(2-Et-PrO)-Ph] H H 1-376 H H H Me 2 —(CH₂)₄—O-(3-iBuO-Ph) HH 1-377 H H H Me 2 —(CH₂)₄—O-(4-iBuO-Ph) H H 1-378 H H H Me 2—(CH₂)₄—O-(3-MeS-Ph) H H 1-379 H H H Me 2 —(CH₂)₄—O-(4-MeS-Ph) H H 1-380H H H Me 2 —(CH₂)₄—O-(3-EtS-Ph) H H 1-381 H H H Me 2—(CH₂)₄—O-(4-EtS-Ph) H H 1-382 H H H Me 2 —(CH₂)₄—O-(3-PrS-Ph) H H 1-383H H H Me 2 —(CH₂)₄—O-(4-PrS-Ph) H H 1-384 H H H Me 2—(CH₂)₄—O-(3-iPrS-Ph) H H 1-385 H H H Me 2 —(CH₂)₄—O-(4-iPrS-Ph) H H1-386 H H H Me 2 —(CH₂)₄—O-[3-(2-Et-PrS)-Ph] H H 1-387 H H H Me 2—(CH₂)₄—O-[4-(2-Et-PrS)-Ph] H H 1-388 H H H Me 2 —(CH₂)₄—O-(3-iBuS-Ph) HH 1-389 H H H Me 2 —(CH₂)₄—O-(4-iBuS-Ph) H H 1-390 H H H Me 2—(CH₂)₄—O-(3-cHx-Ph) H H 1-391 H H H Me 2 —(CH₂)₄—O-(4-cHx-Ph) H H 1-392H H H Me 2 —(CH₂)₄—O-(3-Ph-Ph) H H 1-393 H H H Me 2 —(CH₂)₄—O-(4-Ph-Ph)H H 1-394 H H H Me 2 —(CH₂)₄—O-(2,4-diMe-Ph) H H 1-395 H H H Me 2—(CH₂)₄—O-(3,4-diMe-Ph) H H 1-396 H H H Me 2 —(CH₂)₄—O-(3,5-diMe-Ph) H H1-397 H H H Me 2 —(CH₂)₅—O-cHx H H 1-398 H H H Me 2 —(CH₂)₅—O-Ph H H1-399 H H H Me 2 —(CH₂)₆—O-cHx H H 1-400 H H H Me 2 —(CH₂)₆—O-Ph H H1-401 H H H Me 2 —(CH₂)₃—OCH₂-cHx H H 1-402 H H H Me 2—(CH₂)₃—OCH₂-(4-F-cHx) H H 1-403 H H H Me 2 —(CH₂)₃—OCH₂-(4-Me-cHx) H H1-404 H H H Me 2 —(CH₂)₃—OCH₂-(4-Et-cHx) H H 1-405 H H H Me 2—(CH₂)₃—OCH₂-(4-CF₃-cHx) H H 1-406 H H H Me 2 —(CH₂)₃—OCH₂-(4-MeO-cHx) HH 1-407 H H H Me 2 —(CH₂)₃—OCH₂-(4-EtO-cHx) H H 1-408 H H H Me 2—(CH₂)₃—OCH₂-(4-MeS-cHx) H H 1-409 H H H Me 2 —(CH₂)₃—OCH₂-(4-cHx-cHx) HH 1-410 H H H Me 2 —(CH₂)₃—OCH₂-(4-Ph-cHx) H H 1-411 H H H Me 2—(CH₂)₃—OCH₂-Ph H H 1-412 H H H Me 2 —(CH₂)₃—OCH₂-(4-F-Ph) H H 1-413 H HH Me 2 —(CH₂)₃—OCH₂-(4-Me-Ph) H H 1-414 H H H Me 2—(CH₂)₃—OCH₂-(4-Et-Ph) H H 1-415 H H H Me 2 —(CH₂)₃—OCH₂-(4-CF₃-Ph) H H1-416 H H H Me 2 —(CH₂)₃—OCH₂-(4-MeO-Ph) H H 1-417 H H H Me 2—(CH₂)₃—OCH₂-(4-EtO-Ph) H H 1-418 H H H Me 2 —(CH₂)₃—OCH₂-(4-MeS-Ph) H H1-419 H H H Me 2 —(CH₂)₃—OCH₂-(4-cHx-Ph) H H 1-420 H H H Me 2—(CH₂)₃—OCH₂-(4-Ph-Ph) H H 1-421 H H H Me 2 —(CH₂)₄—OCH₂-cPn H H 1-422 HH H Me 2 —(CH₂)₄—OCH₂-cHx H H 1-423 H H H Me 2 —(CH₂)₄—OCH₂-cHx Me H1-424 H H H Me 2 —(CH₂)₄—OCH₂-cHx H Me 1-425 H H H Me 2 —(CH₂)₄—OCH₂-cHxF H 1-426 H H H Me 2 —(CH₂)₄—OCH₂-cHx H F 1-427 H H H Me 2—(CH₂)₄—OCH₂-(3-F-cHx) H H 1-428 H H H Me 2 —(CH₂)₄—OCH₂-(4-F-cHx) H H1-429 H H H Me 2 —(CH₂)₄—OCH₂-(4-Cl-cHx) H H 1-430 H H H Me 2—(CH₂)₄—OCH₂-(4-Br-cHx) H H 1-431 H H H Me 2 —(CH₂)₄—OCH₂-(3-Me-cHx) H H1-432 H H H Me 2 —(CH₂)₄—OCH₂-(4-Me-cHx) H H 1-433 H H H Me 2—(CH₂)₄—OCH₂-(3-Et-cHx) H H 1-434 H H H Me 2 —(CH₂)₄—OCH₂-(4-Et-cHx) H H1-435 H H H Me 2 —(CH₂)₄—OCH₂-(3-Pr-cHx) H H 1-436 H H H Me 2—(CH₂)₄—OCH₂-(4-Pr-cHx) H H 1-437 H H H Me 2 —(CH₂)₄—OCH₂-(4-iPr-cHx) HH 1-438 H H H Me 2 —(CH₂)₄—OCH₂-(3-Bu-cHx) H H 1-439 H H H Me 2—(CH₂)₄—OCH₂-(4-Bu-cHx) H H 1-440 H H H Me 2 —(CH₂)₄—OCH₂-(3-CF₃-cHx) HH 1-441 H H H Me 2 —(CH₂)₄—OCH₂-(4-CF₃-cHx) H H 1-442 H H H Me 2—(CH₂)₄—OCH₂-(3-MeO-cHx) H H 1-443 H H H Me 2 —(CH₂)₄—OCH₂-(4-MeO-cHx) HH 1-444 H H H Me 2 —(CH₂)₄—OCH₂-(3-EtO-cHx) H H 1-445 H H H Me 2—(CH₂)₄—OCH₂-(4-EtO-cHx) H H 1-446 H H H Me 2 —(CH₂)₄—OCH₂-(3-PrO-cHx) HH 1-447 H H H Me 2 —(CH₂)₄—OCH₂-(4-PrO-cHx) H H 1-448 H H H Me 2—(CH₂)₄—OCH₂-(3-iPrO-cHx) H H 1-449 H H H Me 2 —(CH₂)₄—OCH₂-(4-iPrO-cHx)H H 1-450 H H H Me 2 —(CH₂)₄—OCH₂-[3-(2-Et-PrO)-cHx] H H 1-451 H H H Me2 —(CH₂)₄—OCH₂-[4-(2-Et-PrO)-cHx] H H 1-452 H H H Me 2—(CH₂)₄—OCH₂-(3-iBuO-cHx) H H 1-453 H H H Me 2 —(CH₂)₄—OCH₂-(4-iBuO-cHx)H H 1-454 H H H Me 2 —(CH₂)₄—OCH₂-(3-MeS-cHx) H H 1-455 H H H Me 2—(CH₂)₄—OCH₂-(4-MeS-cHx) H H 1-456 H H H Me 2 —(CH₂)₄—OCH₂-(3-EtS-cHx) HH 1-457 H H H Me 2 —(CH₂)₄—OCH₂-(4-EtS-cHx) H H 1-458 H H H Me 2—(CH₂)₄—OCH₂-(3-PrS-cHx) H H 1-459 H H H Me 2 —(CH₂)₄—OCH₂-(4-PrS-cHx) HH 1-460 H H H Me 2 —(CH₂)₄—OCH₂-(3-iPrS-cHx) H H 1-461 H H H Me 2—(CH₂)₄—OCH₂-(4-iPrS-cHx) H H 1-462 H H H Me 2—(CH₂)₄—OCH₂-[3-(2-Et-PrS)-cHx] H H 1-463 H H H Me 2—(CH₂)₄—OCH₂-[4-(2-Et-PrS)-cHx] H H 1-464 H H H Me 2—(CH₂)₄—OCH₂-(3-iBuS-cHx) H H 1-465 H H H Me 2 —(CH₂)₄—OCH₂-(4-iBuS-cHx)H H 1-466 H H H Me 2 —(CH₂)₄—OCH₂-(3-cHx-cHx) H H 1-467 H H H Me 2—(CH₂)₄—OCH₂-(4-cHx-cHx) H H 1-468 H H H Me 2 —(CH₂)₄—OCH₂-(3-Ph-cHx) HH 1-469 H H H Me 2 —(CH₂)₄—OCH₂-(4-Ph-cHx) H H 1-470 H H H Me 2—(CH₂)₄—OCH₂-(2,4-diMe-cHx) H H 1-471 H H H Me 2—(CH₂)₄—OCH₂-(3,4-diMe-cHx) H H 1-472 H H H Me 2—(CH₂)₄—OCH₂-(3,5-diMe-cHx) H H 1-473 H H H Me 2 —(CH₂)₄—OCH₂-Ph H H1-474 H H H Me 2 —(CH₂)₄—OCH₂-Ph Me H 1-475 H H H Me 2 —(CH₂)₄—OCH₂-Ph HMe 1-476 H H H Me 2 —(CH₂)₄—OCH₂-Ph F H 1-477 H H H Me 2 —(CH₂)₄—OCH₂-PhH F 1-478 H H H Me 2 —(CH₂)₄—OCH₂-(3-F-Ph) H H 1-479 H H H Me 2—(CH₂)₄—OCH₂-(4-F-Ph) H H 1-480 H H H Me 2 —(CH₂)₄—OCH₂-(4-Cl-Ph) H H1-481 H H H Me 2 —(CH₂)₄—OCH₂-(4-Br-Ph) H H 1-482 H H H Me 2—(CH₂)₄—OCH₂-(3-Me-Ph) H H 1-483 H H H Me 2 —(CH₂)₄—OCH₂-(4-Me-Ph) H H1-484 H H H Me 2 —(CH₂)₄—OCH₂-(3-Et-Ph) H H 1-485 H H H Me 2—(CH₂)₄—OCH₂-(4-Et-Ph) H H 1-486 H H H Me 2 —(CH₂)₄—OCH₂-(3-Pr-Ph) H H1-487 H H H Me 2 —(CH₂)₄—OCH₂-(4-Pr-Ph) H H 1-488 H H H Me 2—(CH₂)₄—OCH₂-(3-iPr-Ph) H H 1-489 H H H Me 2 —(CH₂)₄—OCH₂-(4-iPr-Ph) H H1-490 H H H Me 2 —(CH₂)₄—OCH₂-(3-Bu-Ph) H H 1-491 H H H Me 2—(CH₂)₄—OCH₂-(4-Bu-Ph) H H 1-492 H H H Me 2 —(CH₂)₄—OCH₂-(3-CF₃-Ph) H H1-493 H H H Me 2 —(CH₂)₄—OCH₂-(4-CF₃-Ph) H H 1-494 H H H Me 2—(CH₂)₄—OCH₂-(3-MeO-Ph) H H 1-495 H H H Me 2 —(CH₂)₄—OCH₂-(4-MeO-Ph) H H1-496 H H H Me 2 —(CH₂)₄—OCH₂-(3-EtO-Ph) H H 1-497 H H H Me 2—(CH₂)₄—OCH₂-(4-EtO-Ph) H H 1-498 H H H Me 2 —(CH₂)₄—OCH₂-(3-PrO-Ph) H H1-499 H H H Me 2 —(CH₂)₄—OCH₂-(4-PrO-Ph) H H 1-500 H H H Me 2—(CH₂)₄—OCH₂-(3-iPrO-Ph) H H 1-501 H H H Me 2 —(CH₂)₄—OCH₂-(4-iPrO-Ph) HH 1-502 H H H Me 2 —(CH₂)₄—OCH₂-[3-(2-Et-PrO)-Ph] H H 1-503 H H H Me 2—(CH₂)₄—OCH₂-[4-(2-Et-PrO)-Ph] H H 1-504 H H H Me 2—(CH₂)₄—OCH₂-(3-iBuO-Ph) H H 1-505 H H H Me 2 —(CH₂)₄—OCH₂-(4-iBuO-Ph) HH 1-506 H H H Me 2 —(CH₂)₄—OCH₂-(3-MeS-Ph) H H 1-507 H H H Me 2—(CH₂)₄—OCH₂-(4-MeS-Ph) H H 1-508 H H H Me 2 —(CH₂)₄—OCH₂-(3-EtS-Ph) H H1-509 H H H Me 2 —(CH₂)₄—OCH₂-(4-EtS-Ph) H H 1-510 H H H Me 2—(CH₂)₄—OCH₂-(3-PrS-Ph) H H 1-511 H H H Me 2 —(CH₂)₄—OCH₂-(4-PrS-Ph) H H1-512 H H H Me 2 —(CH₂)₄—OCH₂-(3-iPrS-Ph) H H 1-513 H H H Me 2—(CH₂)₄—OCH₂-(4-iPrS-Ph) H H 1-514 H H H Me 2—(CH₂)₄—OCH₂-[3-(2-Et-PrS)-Ph] H H 1-515 H H H Me 2—(CH₂)₄—OCH₂-[4-(2-Et-PrS)-Ph] H H 1-516 H H H Me 2—(CH₂)₄—OCH₂-(3-iBuS-Ph) H H 1-517 H H H Me 2 —(CH₂)₄—OCH₂-(4-iBuS-Ph) HH 1-518 H H H Me 2 —(CH₂)₄—OCH₂-(3-cHx-Ph) H H 1-519 H H H Me 2—(CH₂)₄—OCH₂-(4-cHx-Ph) H H 1-520 H H H Me 2 —(CH₂)₄—OCH₂-(3-Ph-Ph) H H1-521 H H H Me 2 —(CH₂)₄—OCH₂-(4-Ph-Ph) H H 1-522 H H H Me 2—(CH₂)₄—OCH₂-(2,4-diMe-Ph) H H 1-523 H H H Me 2—(CH₂)₄—OCH₂-(3,4-diMe-Ph) H H 1-524 H H H Me 2—(CH₂)₄—OCH₂-(3,5-diMe-Ph) H H 1-525 H H H Me 2 —(CH₂)₅—OCH₂-cHx H H1-526 H H H Me 2 —(CH₂)₅—OCH₂-Ph H H 1-527 H H H Me 2 —(CH₂)₆—OCH₂-cHx HH 1-528 H H H Me 2 —(CH₂)₆—OCH₂-Ph H H 1-529 H H H Me 2 —C≡C-cHX H H1-530 H H H Me 2 —C≡C-(4-F-cHx) H H 1-531 H H H Me 2 —C≡C-(4-Me-cHx) H H1-532 H H H Me 2 —C≡C-(4-Et-cHx) H H 1-533 H H H Me 2 —C≡C-(4-CF₃-cHx) HH 1-534 H H H Me 2 —C≡C-(4-MeO-cHx) H H 1-535 H H H Me 2—C≡C-(4-EtO-cHx) H H 1-536 H H H Me 2 —C≡C-(4-MeS-cHx) H H 1-537 H H HMe 2 —C≡C-(4-cHx-cHx) H H 1-538 H H H Me 2 —C≡C-(4-Ph-cHx) H H 1-539 H HH Me 2 —C≡C-Ph H H 1-540 H H H Me 2 —C≡C-(4-F-Ph) H H 1-541 H H H Me 2—C≡C-(4-Me-Ph) H H 1-542 H H H Me 2 —C≡C-(4-Pr-Ph) H H 1-543 H H H Me 2—C≡C-(4-Bu-Ph) H H 1-544 H H H Me 2 —C≡C-(4-MeO-Ph) H H 1-545 H H H Me 2—C≡C-(4-EtO-Ph) H H 1-546 H H H Me 2 —C≡C-(4-PrO-Ph) H H 1-547 H H H Me2 —C≡C-(4-cHx-Ph) H H 1-548 H H H Me 2 —C≡C-(4-Ph-Ph) H H 1-549 H H H Me2 —C≡C—(CH₂)₂-cHx H H 1-550 H H H Me 2 —C≡C—(CH₂)₂-(4-F-cHx) H H 1-551 HH H Me 2 —C≡C—(CH₂)₂-(4-Me-cHx) H H 1-552 H H H Me 2—C≡C—(CH₂)₂-(4-Et-cHx) H H 1-553 H H H Me 2 —C≡C—(CH₂)₂-(4-CF₃-cHx) H H1-554 H H H Me 2 —C≡C—(CH₂)₂-(4-MeO-cHx) H H 1-555 H H H Me 2—C≡C—(CH₂)₂-(4-EtO-cHx) H H 1-556 H H H Me 2 —C≡C—(CH₂)₂-(4-MeS-cHx) H H1-557 H H H Me 2 —C≡C—(CH₂)₂-(4-cHx-cHx) H H 1-558 H H H Me 2—C≡C—(CH₂)₂-(4-Ph-cHx) H H 1-559 H H H Me 2 —C≡C—(CH₂)₂-Ph H H 1-560 H HH Me 2 —C≡C—(CH₂)₂-(4-F-Ph) H H 1-561 H H H Me 2 —C≡C—(CH₂)₂-(4-Me-Ph) HH 1-562 H H H Me 2 —C≡C—(CH₂)₂-(4-Et-Ph) H H 1-563 H H H Me 2—C≡C—(CH₂)₂-(4-CF₃-Ph) H H 1-564 H H H Me 2 —C≡C—(CH₂)₂-(4-MeO-Ph) H H1-565 H H H Me 2 —C≡C—(CH₂)₂-(4-EtO-Ph) H H 1-566 H H H Me 2—C≡C—(CH₂)₂-(4-MeS-Ph) H H 1-567 H H H Me 2 —C≡C—(CH₂)₂-(4-cHx-Ph) H H1-568 H H H Me 2 —C≡C—(CH₂)₂-(4-Ph-Ph) H H 1-569 H H H Me 2—C≡C—(CH₂)₃-cPn H H 1-570 H H H Me 2 —C≡C—(CH₂)₃-cHx H H 1-571 H H H Me2 —C≡C—(CH₂)₃-cHx Me H 1-572 H H H Me 2 —C≡C—(CH₂)₃-cHx H Me 1-573 H H HMe 2 —C≡C—(CH₂)₃-cHx F H 1-574 H H H Me 2 —C≡C—(CH₂)₃-cHx H F 1-575 H HH Me 2 —C≡C—(CH₂)₃-(3-F-cHx) H H 1-576 H H H Me 2 —C≡C—(CH₂)₃-(4-F-cHx)H H 1-577 H H H Me 2 —C≡C—(CH₂)₃-(4-Cl-cHx) H H 1-578 H H H Me 2—C≡C—(CH₂)₃-(4-Br-cHx) H H 1-579 H H H Me 2 —C≡C—(CH₂)₃-(3-Me-cHx) H H1-580 H H H Me 2 —C≡C—(CH₂)₃-(4-Me-cHx) H H 1-581 H H H Me 2—C≡C—(CH₂)₃-(3-Et-cHx) H H 1-582 H H H Me 2 —C≡C—(CH₂)₃-(4-Et-cHx) H H1-583 H H H Me 2 —C≡C—(CH₂)₃-(3-Pr-cHx) H H 1-584 H H H Me 2—C≡C—(CH₂)₃-(4-Pr-cHx) H H 1-585 H H H Me 2 —C≡C—(CH₂)₃-(4-iPr-cHx) H H1-586 H H H Me 2 —C≡C—(CH₂)₃-(3-Bu-cHx) H H 1-587 H H H Me 2—C≡C—(CH₂)₃-(4-Bu-cHx) H H 1-588 H H H Me 2 —C≡C—(CH₂)₃-(3-CF₃-cHx) H H1-589 H H H Me 2 —C≡C—(CH₂)₃-(4-CF₃-cHx) H H 1-590 H H H Me 2—C≡C—(CH₂)₃-(3-MeO-cHx) H H 1-591 H H H Me 2 —C≡C—(CH₂)₃-(4-MeO-cHx) H H1-592 H H H Me 2 —C≡C—(CH₂)₃-(3-EtO-cHx) H H 1-593 H H H Me 2—C≡C—(CH₂)₃-(4-EtO-cHx) H H 1-594 H H H Me 2 —C≡C—(CH₂)₃-(3-PrO-cHx) H H1-595 H H H Me 2 —C≡C—(CH₂)₃-(4-PrO-cHx) H H 1-596 H H H Me 2—C≡C—(CH₂)₃-(3-iPrO-cHx) H H 1-597 H H H Me 2 —C≡C—(CH₂)₃-(4-iPrO-cHx) HH 1-598 H H H Me 2 —C≡C—(CH₂)₃-[3-(2-Et-PrO)-cHx] H H 1-599 H H H Me 2—C≡C—(CH₂)₃-[4-(2-Et-PrO)-cHx] H H 1-600 H H H Me 2—C≡C—(CH₂)₃-(3-iBuO-cHx) H H 1-601 H H H Me 2 —C≡C—(CH₂)₃-(4-iBuO-cHx) HH 1-602 H H H Me 2 —C≡C—(CH₂)₃-(3-MeS-cHx) H H 1-603 H H H Me 2—C≡C—(CH₂)₃-(4-MeS-cHx) H H 1-604 H H H Me 2 —C≡C—(CH₂)₃-(3-EtS-cHx) H H1-605 H H H Me 2 —C≡C—(CH₂)₃-(4-EtS-cHx) H H 1-606 H H H Me 2—C≡C—(CH₂)₃-(3-PrS-cHx) H H 1-607 H H H Me 2 —C≡C—(CH₂)₃-(4-PrS-cHx) H H1-608 H H H Me 2 —C≡C—(CH₂)₃-(3-iPrS-cHx) H H 1-609 H H H Me 2—C≡C—(CH₂)₃-(4-iPrS-cHx) H H 1-610 H H H Me 2—C≡C—(CH₂)₃-[3-(2-Et-PrS)-cHx] H H 1-611 H H H Me 2—C≡C—(CH₂)₃-[4-(2-Et-PrS)-cHx] H H 1-612 H H H Me 2—C≡C—(CH₂)₃-(3-iBuS-cHx) H H 1-613 H H H Me 2 —C≡C—(CH₂)₃-(4-iBuS-cHx) HH 1-614 H H H Me 2 —C≡C—(CH₂)₃-(3-cHx-cHx) H H 1-615 H H H Me 2—C≡C—(CH₂)₃-(4-cHx-cHx) H H 1-616 H H H Me 2 —C≡C—(CH₂)₃-(3-Ph-cHx) H H1-617 H H H Me 2 —C≡C—(CH₂)₃-(4-Ph-cHx) H H 1-618 H H H Me 2—C≡C—(CH₂)₃-(2,4-diMe-cHx) H H 1-619 H H H Me 2—C≡C—(CH₂)₃-(3,4-diMe-cHx) H H 1-620 H H H Me 2—C≡C—(CH₂)₃-(3,5-diMe-cHx) H H 1-621 H H H Me 2 —C≡C—(CH₂)₃-Ph H H 1-622H H H Me 2 —C≡C—(CH₂)₃-Ph Me H 1-623 H H H Me 2 —C≡C—(CH₂)₃-Ph H Me1-624 H H H Me 2 —C≡C—(CH₂)₃-Ph F H 1-625 H H H Me 2 —C≡C—(CH₂)₃-Ph H F1-626 H H H Me 2 —C≡C—(CH₂)₃-(3-F-Ph) H H 1-627 H H H Me 2—C≡C—(CH₂)₃-(4-F-Ph) H H 1-628 H H H Me 2 —C≡C—(CH₂)₃-(4-Cl-Ph) H H1-629 H H H Me 2 —C≡C—(CH₂)₃-(4-Br-Ph) H H 1-630 H H H Me 2—C≡C—(CH₂)₃-(3-Me-Ph) H H 1-631 H H H Me 2 —C≡C—(CH₂)₃-(4-Me-Ph) H H1-632 H H H Me 2 —C≡C—(CH₂)₃-(3-Et-Ph) H H 1-633 H H H Me 2—C≡C—(CH₂)₃-(4-Et-Ph) H H 1-634 H H H Me 2 —C≡C—(CH₂)₃-(3-Pr-Ph) H H1-635 H H H Me 2 —C≡C—(CH₂)₃-(4-Pr-Ph) H H 1-636 H H H Me 2—C≡C—(CH₂)₃-(3-iPr-Ph) H H 1-637 H H H Me 2 —C≡C—(CH₂)₃-(4-iPr-Ph) H H1-638 H H H Me 2 —C≡C—(CH₂)₃-(3-Bu-Ph) H H 1-639 H H H Me 2—C≡C—(CH₂)₃-(4-Bu-Ph) H H 1-640 H H H Me 2 —C≡C—(CH₂)₃-(3-CF₃-Ph) H H1-641 H H H Me 2 —C≡C—(CH₂)₃-(4-CF₃-Ph) H H 1-642 H H H Me 2—C≡C—(CH₂)₃-(3-MeO-Ph) H H 1-643 H H H Me 2 —C≡C—(CH₂)₃-(4-MeO-Ph) H H1-644 H H H Me 2 —C≡C—(CH₂)₃-(3-EtO-Ph) H H 1-645 H H H Me 2—C≡C—(CH₂)₃-(4-EtO-Ph) H H 1-646 H H H Me 2 —C≡C—(CH₂)₃-(3-PrO-Ph) H H1-647 H H H Me 2 —C≡C—(CH₂)₃-(4-PrO-Ph) H H 1-648 H H H Me 2—C≡C—(CH₂)₃-(3-iPrO-Ph) H H 1-649 H H H Me 2 —C≡C—(CH₂)₃-(4-iPrO-Ph) H H1-650 H H H Me 2 —C≡C—(CH₂)₃-[3-(2-Et-PrO)-Ph] H H 1-651 H H H Me 2—C≡C—(CH₂)₃-[4-(2-Et-PrO)-Ph] H H 1-652 H H H Me 2—C≡C—(CH₂)₃-(3-iBuO-Ph) H H 1-653 H H H Me 2 —C≡C—(CH₂)₃-(4-iBuO-Ph) H H1-654 H H H Me 2 —C≡C—(CH₂)₃-(3-MeS-Ph) H H 1-655 H H H Me 2—C≡C—(CH₂)₃-(4-MeS-Ph) H H 1-656 H H H Me 2 —C≡C—(CH₂)₃-(3-EtS-Ph) H H1-657 H H H Me 2 —C≡C—(CH₂)₃-(4-EtS-Ph) H H 1-658 H H H Me 2—C≡C—(CH₂)₃-(3-PrS-Ph) H H 1-659 H H H Me 2 —C≡C—(CH₂)₃-(4-PrS-Ph) H H1-660 H H H Me 2 —C≡C—(CH₂)₃-(3-iPrS-Ph) H H 1-661 H H H Me 2—C≡C—(CH₂)₃-(4-iPrS-Ph) H H 1-662 H H H Me 2—C≡C—(CH₂)₃-[3-(2-Et-PrS)-Ph] H H 1-663 H H H Me 2—C≡C—(CH₂)₃-[4-(2-Et-PrS)-Ph] H H 1-664 H H H Me 2—C≡C—(CH₂)₃-(3-iBuS-Ph) H H 1-665 H H H Me 2 —C≡C—(CH₂)₃-(4-iBuS-Ph) H H1-666 H H H Me 2 —C≡C—(CH₂)₃-(3-cHx-Ph) H H 1-667 H H H Me 2—C≡C—(CH₂)₃-(4-cHx-Ph) H H 1-668 H H H Me 2 —C≡C—(CH₂)₃-(3-Ph-Ph) H H1-669 H H H Me 2 —C≡C—(CH₂)₃-(4-Ph-Ph) H H 1-670 H H H Me 2—C≡C—(CH₂)₃-(2,4-diMe-Ph) H H 1-671 H H H Me 2 —C≡C—(CH₂)₃-(3,4-diMe-Ph)H H 1-672 H H H Me 2 —C≡C—(CH₂)₃-(3,5-diMe-Ph) H H 1-673 H H H Me 2—C≡C—(CH₂)₃-Np(1) H H 1-674 H H H Me 2 —C≡C—(CH₂)₃-Np(2) H H 1-675 H H HMe 2 —C≡C—(CH₂)₄-cPn H H 1-676 H H H Me 2 —C≡C—(CH₂)₄-cHx H H 1-677 H HH Me 2 —C≡C—(CH₂)₄-cHx Me H 1-678 H H H Me 2 —C≡C—(CH₂)₄-cHx H Me 1-679H H H Me 2 —C≡C—(CH₂)₄-cHx F H 1-680 H H H Me 2 —C≡C—(CH₂)₄-cHx H F1-681 H H H Me 2 —C≡C—(CH₂)₄-(3-F-cHx) H H 1-682 H H H Me 2—C≡C—(CH₂)₄-(4-F-cHx) H H 1-683 H H H Me 2 —C≡C—(CH₂)₄-(4-Cl-cHx) H H1-684 H H H Me 2 —C≡C—(CH₂)₄-(4-Br-cHx) H H 1-685 H H H Me 2—C≡C—(CH₂)₄-(3-Me-cHx) H H 1-686 H H H Me 2 —C≡C—(CH₂)₄-(4-Me-cHx) H H1-687 H H H Me 2 —C≡C—(CH₂)₄-(3-Et-cHx) H H 1-688 H H H Me 2—C≡C—(CH₂)₄-(4-Et-cHx) H H 1-689 H H H Me 2 —C≡C—(CH₂)₄-(3-Pr-cHx) H H1-690 H H H Me 2 —C≡C—(CH₂)₄-(4-Pr-cHx) H H 1-691 H H H Me 2—C≡C—(CH₂)₄-(4-iPr-cHx) H H 1-692 H H H Me 2 —C≡C—(CH₂)₄-(3-Bu-cHx) H H1-693 H H H Me 2 —C≡C—(CH₂)₄-(4-Bu-cHx) H H 1-694 H H H Me 2—C≡C—(CH₂)₄-(3-CF₃-cHx) H H 1-695 H H H Me 2 —C≡C—(CH₂)₄-(4-CF₃-cHx) H H1-696 H H H Me 2 —C≡C—(CH₂)₄-(3-MeO-cHx) H H 1-697 H H H Me 2—C≡C—(CH₂)₄-(4-MeO-cHx) H H 1-698 H H H Me 2 —C≡C—(CH₂)₄-(3-EtO-cHx) H H1-699 H H H Me 2 —C≡C—(CH₂)₄-(4-EtO-cHx) H H 1-700 H H H Me 2—C≡C—(CH₂)₄-(3-PrO-cHx) H H 1-701 H H H Me 2 —C≡C—(CH₂)₄-(4-PrO-cHx) H H1-702 H H H Me 2 —C≡C—(CH₂)₄-(3-iPrO-cHx) H H 1-703 H H H Me 2—C≡C—(CH₂)₄-(4-iPrO-cHx) H H 1-704 H H H Me 2—C≡C—(CH₂)₄-[3-(2-Et-PrO)-cHx] H H 1-705 H H H Me 2—C≡C—(CH₂)₄-[4-(2-Et-PrO)-cHx] H H 1-706 H H H Me 2—C≡C—(CH₂)₄-(3-iBuO-cHx) H H 1-707 H H H Me 2 —C≡C—(CH₂)₄-(4-iBuO-cHx) HH 1-708 H H H Me 2 —C≡C—(CH₂)₄-(3-MeS-cHx) H H 1-709 H H H Me 2—C≡C—(CH₂)₄-(4-MeS-cHx) H H 1-710 H H H Me 2 —C≡C—(CH₂)₄-(3-EtS-cHx) H H1-711 H H H Me 2 —C≡C—(CH₂)₄-(4-EtS-cHx) H H 1-712 H H H Me 2—C≡C—(CH₂)₄-(3-PrS-cHx) H H 1-713 H H H Me 2 —C≡C—(CH₂)₄-(4-PrS-cHx) H H1-714 H H H Me 2 —C≡C—(CH₂)₄-(3-iPrS-cHx) H H 1-715 H H H Me 2—C≡C—(CH₂)₄-(4-iPrS-cHx) H H 1-716 H H H Me 2—C≡C—(CH₂)₄-[3-(2-Et-PrS)-cHx] H H 1-717 H H H Me 2—C≡C—(CH₂)₄-[4-(2-Et-PrS)-cHx] H H 1-718 H H H Me 2—C≡C—(CH₂)₄-(3-iBuS-cHx) H H 1-719 H H H Me 2 —C≡C—(CH₂)₄-(4-iBuS-cHx) HH 1-720 H H H Me 2 —C≡C—(CH₂)₄-(3-cHx-cHx) H H 1-721 H H H Me 2—C≡C—(CH₂)₄-(4-cHx-cHx) H H 1-722 H H H Me 2 —C≡C—(CH₂)₄-(3-Ph-cHx) H H1-723 H H H Me 2 —C≡C—(CH₂)₄-(4-Ph-cHx) H H 1-724 H H H Me 2—C≡C—(CH₂)₄-(2,4-diMe-cHx) H H 1-725 H H H Me 2—C≡C—(CH₂)₄-(3,4-diMe-cHx) H H 1-726 H H H Me 2—C≡C—(CH₂)₄-(3,5-diMe-cHx) H H 1-727 H H H Me 2 —C≡C—(CH₂)₄-Ph H H 1-728H H H Me 2 —C≡C—(CH₂)₄-Ph Me H 1-729 H H H Me 2 —C≡C—(CH₂)₄-Ph H Me1-730 H H H Me 2 —C≡C—(CH₂)₄-Ph F H 1-731 H H H Me 2 —C≡C—(CH₂)₄-Ph H F1-732 H H H Me 2 —C≡C—(CH₂)₄-(3-F-Ph) H H 1-733 H H H Me 2—C≡C—(CH₂)₄-(4-F-Ph) H H 1-734 H H H Me 2 —C≡C—(CH₂)₄-(4-Cl-Ph) H H1-735 H H H Me 2 —C≡C—(CH₂)₄-(4-Br-Ph) H H 1-736 H H H Me 2—C≡C—(CH₂)₄-(3-Me-Ph) H H 1-737 H H H Me 2 —C≡C—(CH₂)₄-(4-Me-Ph) H H1-738 H H H Me 2 —C≡C—(CH₂)₄-(3-Et-Ph) H H 1-739 H H H Me 2—C≡C—(CH₂)₄-(4-Et-Ph) H H 1-740 H H H Me 2 —C≡C—(CH₂)₄-(3-Pr-Ph) H H1-741 H H H Me 2 —C≡C—(CH₂)₄-(4-Pr-Ph) H H 1-742 H H H Me 2—C≡C—(CH₂)₄-(3-iPr-Ph) H H 1-743 H H H Me 2 —C≡C—(CH₂)₄-(4-iPr-Ph) H H1-744 H H H Me 2 —C≡C—(CH₂)₄-(3-Bu-Ph) H H 1-745 H H H Me 2—C≡C—(CH₂)₄-(4-Bu-Ph) H H 1-746 H H H Me 2 —C≡C—(CH₂)₄-(3-CF₃-Ph) H H1-747 H H H Me 2 —C≡C—(CH₂)₄-(4-CF₃-Ph) H H 1-748 H H H Me 2—C≡C—(CH₂)₄-(3-MeO-Ph) H H 1-749 H H H Me 2 —C≡C—(CH₂)₄-(4-MeO-Ph) H H1-750 H H H Me 2 —C≡C—(CH₂)₄-(3-EtO-Ph) H H 1-751 H H H Me 2—C≡C—(CH₂)₄-(4-Eto-Ph) H H 1-752 H H H Me 2 —C≡C—(CH₂)₄-(3-PrO-Ph) H H1-753 H H H Me 2 —C≡C—(CH₂)₄-(4-PrO-Ph) H H 1-754 H H H Me 2—C≡C—(CH₂)₄-(3-iPrO-Ph) H H 1-755 H H H Me 2 —C≡C—(CH₂)₄-(4-iPrO-Ph) H H1-756 H H H Me 2 —C≡C—(CH₂)₄-[3-(2-Et-PrO)-Ph] H H 1-757 H H H Me 2—C≡C—(CH₂)₄-[4-(2-Et-PrO)-Ph] H H 1-758 H H H Me 2—C≡C—(CH₂)₄-(3-iBuO-Ph) H H 1-759 H H H Me 2 —C≡C—(CH₂)₄-(4-iBuO-Ph) H H1-760 H H H Me 2 —C≡C—(CH₂)₄-(3-MeS-Ph) H H 1-761 H H H Me 2—C≡C—(CH₂)₄-(4-MeS-Ph) H H 1-762 H H H Me 2 —C≡C—(CH₂)₄-(3-EtS-Ph) H H1-763 H H H Me 2 —C≡C—(CH₂)₄-(4-EtS-Ph) H H 1-764 H H H Me 2—C≡C—(CH₂)₄-(3-PrS-Ph) H H 1-765 H H H Me 2 —C≡C—(CH₂)₄-(4-PrS-Ph) H H1-766 H H H Me 2 —C≡C—(CH₂)₄-(3-iPrS-Ph) H H 1-767 H H H Me 2—C≡C—(CH₂)₄-(4-iPrS-Ph) H H 1-768 H H H Me 2—C≡C—(CH₂)₄-[3-(2-Et-PrS)-Ph] H H 1-769 H H H Me 2—C≡C—(CH₂)₄-[4-(2-Et-PrS)-Ph] H H 1-770 H H H Me 2—C≡C—(CH₂)₄-(3-iBuS-Ph) H H 1-771 H H H Me 2 —C≡C—(CH₂)₄-(4-iBuS-Ph) H H1-772 H H H Me 2 —C≡C—(CH₂)₄-(3-cHx-Ph) H H 1-773 H H H Me 2—C≡C—(CH₂)₄-(4-cHx-Ph) H H 1-774 H H H Me 2 —C≡C—(CH₂)₄-(3-Ph-Ph) H H1-775 H H H Me 2 —C≡C—(CH₂)₄-(4-Ph-Ph) H H 1-776 H H H Me 2—C≡C—(CH₂)₄-(2,4-diMe-Ph) H H 1-777 H H H Me 2 —C≡C—(CH₂)₄-(3,4-diMe-Ph)H H 1-778 H H H Me 2 —C≡C—(CH₂)₄-(3,5-diMe-Ph) H H 1-779 H H H Me 2—C≡C—(CH₂)₄-Np(1) H H 1-780 H H H Me 2 —C≡C—(CH₂)₄-Np(2) H H 1-781 H H HMe 2 —C≡C—(CH₂)₅-cHx H H 1-782 H H H Me 2 —C≡C—(CH₂)₅-(4-F-cHx) H H1-783 H H H Me 2 —C≡C—(CH₂)₅-(4-Me-cHx) H H 1-784 H H H Me 2—C≡C—(CH₂)₅-(4-Et-cHx) H H 1-785 H H H Me 2 —C≡C—(CH₂)₅-(4-CF₃-cHx) H H1-786 H H H Me 2 —C≡C—(CH₂)₅-(4-MeO-cHx) H H 1-787 H H H Me 2—C≡C—(CH₂)₅-(4-EtO-cHx) H H 1-788 H H H Me 2 —C≡C—(CH₂)₅-(4-MeS-cHx) H H1-789 H H H Me 2 —C≡C—(CH₂)₅-(4-cHx-cHx) H H 1-790 H H H Me 2—C≡C—(CH₂)₅-(4-Ph-cHx) H H 1-791 H H H Me 2 —C≡C—(CH₂)₅-Ph H H 1-792 H HH Me 2 —C≡C—(CH₂)₅-(4-F-Ph) H H 1-793 H H H Me 2 —C≡C—(CH₂)₅-(4-Me-Ph) HH 1-794 H H H Me 2 —C≡C—(CH₂)₅-(4-Et-Ph) H H 1-795 H H H Me 2—C≡C—(CH₂)₅-(4-CF₃-Ph) H H 1-796 H H H Me 2 —C≡C—(CH₂)₅-(4-MeO-Ph) H H1-797 H H H Me 2 —C≡C—(CH₂)₅-(4-EtO-Ph) H H 1-798 H H H Me 2—C≡C—(CH₂)₅-(4-MeS-Ph) H H 1-799 H H H Me 2 —C≡C—(CH₂)₅-(4-cHx-Ph) H H1-800 H H H Me 2 —C≡C—(CH₂)₅-(4-Ph-Ph) H H 1-801 H H H Me 2—C≡C—(CH₂)₆-cHx H H 1-802 H H H Me 2 —C≡C—(CH₂)₆-(4-F-cHx) H H 1-803 H HH Me 2 —C≡C—(CH₂)₆-(4-Me-cHx) H H 1-804 H H H Me 2—C≡C—(CH₂)₆-(4-Et-cHx) H H 1-805 H H H Me 2 —C≡C—(CH₂)₆-(4-CF₃-cHx) H H1-806 H H H Me 2 —C≡C—(CH₂)₆-(4-MeO-cHx) H H 1-807 H H H Me 2—C≡C—(CH₂)₆-(4-EtO-cHx) H H 1-808 H H H Me 2 —C≡C—(CH₂)₆-(4-MeS-cHx) H H1-809 H H H Me 2 —C≡C—(CH₂)₆-(4-cHx-cHx) H H 1-810 H H H Me 2—C≡C—(CH₂)₆-(4-Ph-cHx) H H 1-811 H H H Me 2 —C≡C—(CH₂)₆-Ph H H 1-812 H HH Me 2 —C≡C—(CH₂)₆-(4-F-Ph) H H 1-813 H H H Me 2 —C≡C—(CH₂)₆-(4-Me-Ph) HH 1-814 H H H Me 2 —C≡C—(CH₂)₆-(4-Et-Ph) H H 1-815 H H H Me 2—C≡C—(CH₂)₆-(4-CF₃-Ph) H H 1-816 H H H Me 2 —C═C—(CH₂)₆-(4-MeO-Ph) H H1-817 H H H Me 2 —C≡C—(CH₂)₆-(4-EtO-Ph) H H 1-818 H H H Me 2—C≡C—(CH₂)₆-(4-MeS-Ph) H H 1-819 H H H Me 2 —C≡C—(CH₂)₆-(4-cHx-Ph) H H1-820 H H H Me 2 —C≡C—(CH₂)₆-(4-Ph-Ph) H H 1-821 H H H Me 2—C≡C—CH₂—O-cHx H H 1-822 H H H Me 2 —C≡C—CH₂—O-(4-F-cHx) H H 1-823 H H HMe 2 —C≡C—CH₂—O-(4-Me-cHx) H H 1-824 H H H Me 2 —C≡C—CH₂—O-(4-Et-cHx) HH 1-825 H H H Me 2 —C≡C—CH₂—O-(4-CF₃-cHx) H H 1-826 H H H Me 2—C≡C—CH₂—O-(4-MeO-cHx) H H 1-827 H H H Me 2 —C≡C—CH₂—O-(4-EtO-cHx) H H1-828 H H H Me 2 —C≡C—CH₂—O-(4-MeS-cHx) H H 1-829 H H H Me 2—C≡C—CH₂—O-(4-cHx-cHx) H H 1-830 H H H Me 2 —C≡C—CH₂—O-(4-Ph-cHx) H H1-831 H H H Me 2 —C≡C—CH₂—O-Ph H H 1-832 H H H Me 2 —C≡C—CH₂—O-(4-F-Ph)H H 1-833 H H H Me 2 —C≡C—CH₂—O-(4-Me-Ph) H H 1-834 H H H Me 2—C≡C—CH₂—O-(4-Et-Ph) H H 1-835 H H H Me 2 —C≡C—CH₂—O-(4-CF₃-Ph) H H1-836 H H H Me 2 —C≡C—CH₂—O-(4-MeO-Ph) H H 1-837 H H H Me 2—C≡C—CH₂—O-(4-EtO-Ph) H H 1-838 H H H Me 2 —C≡C—CH₂—O-(4-MeS-Ph) H H1-839 H H H Me 2 —C≡C—CH₂—O-(4-cHx-Ph) H H 1-840 H H H Me 2—C≡C—CH₂—O-(4-Ph-Ph) H H 1-841 H H H Me 2 —C≡C—(CH₂)₂O-cPn H H 1-842 H HH Me 2 —C≡C—(CH₂)₂O-cHx H H 1-843 H H H Me 2 —C≡C—(CH₂)₂O-cHx Me H 1-844H H H Me 2 —C≡C—(CH₂)₂O-cHx H Me 1-845 H H H Me 2 —C≡C—(CH₂)₂O-cHx F H1-846 H H H Me 2 —C≡C—(CH₂)₂O-cHx H F 1-847 H H H Me 2—C≡C—(CH₂)₂O-(3-F-cHx) H H 1-848 H H H Me 2 —C≡C—(CH₂)₂O-(4-F-cHx) H H1-849 H H H Me 2 —C≡C—(CH₂)₂O-(4-Cl-cHx) H H 1-850 H H H Me 2—C≡C—(CH₂)₂O-(4-Br-cHx) H H 1-851 H H H Me 2 —C≡C—(CH₂)₂O-(3-Me-cHx) H H1-852 H H H Me 2 —C≡C—(CH₂)₂O-(4-Me-cHx) H H 1-853 H H H Me 2—C≡C—(CH₂)₂O-(3-Et-cHx) H H 1-854 H H H Me 2 —C≡C—(CH₂)₂O-(4-Et-cHx) H H1-855 H H H Me 2 —C≡C—(CH₂)₂O-(3-Pr-cHx) H H 1-856 H H H Me 2—C≡C—(CH₂)₂O-(4-Pr-cHx) H H 1-857 H H H Me 2 —C≡C—(CH₂)₂O-(4-iPr-cHx) HH 1-858 H H H Me 2 —C≡C—(CH₂)₂O-(3-Bu-cHx) H H 1-859 H H H Me 2—C≡C—(CH₂)₂O-(4-Bu-cHx) H H 1-860 H H H Me 2 —C≡C—(CH₂)₂O-(3-CF₃-cHx) HH 1-861 H H H Me 2 —C≡C—(CH₂)₂O-(4-CF₃-cHx) H H 1-862 H H H Me 2—C≡C—(CH₂)₂O-(3-MeO-cHx) H H 1-863 H H H Me 2 —C≡C—(CH₂)₂O-(4-MeO-cHx) HH 1-864 H H H Me 2 —C≡C—(CH₂)₂O-(3-EtO-cHx) H H 1-865 H H H Me 2—C≡C—(CH₂)₂O-(4-EtO-cHx) H H 1-866 H H H Me 2 —C≡C—(CH₂)₂O-(3-PrO-cHx) HH 1-867 H H H Me 2 —C≡C—(CH₂)₂O-(4-PrO-cHx) H H 1-868 H H H Me 2—C≡C—(CH₂)₂O-(3-iPrO-cHx) H H 1-869 H H H Me 2 —C≡C—(CH₂)₂O-(4-iPrO-cHx)H H 1-870 H H H Me 2 —C≡C—(CH₂)₂O-[3-(2-Et-PrO)-cHx] H H 1-871 H H H Me2 —C≡C—(CH₂)₂O-[4-(2-Et-PrO)-cHx] H H 1-872 H H H Me 2—C≡C—(CH₂)₂O-(3-iBuO-cHx) H H 1-873 H H H Me 2 —C≡C—(CH₂)₂O-(4-iBuO-cHx)H H 1-874 H H H Me 2 —C≡C—(CH₂)₂O-(3-MeS-cHx) H H 1-875 H H H Me 2—C≡C—(CH₂)₂O-(4-MeS-cHx) H H 1-876 H H H Me 2 —C≡C—(CH₂)₂O-(3-EtS-cHx) HH 1-877 H H H Me 2 —C≡C—(CH₂)₂O-(4-EtS-cHx) H H 1-878 H H H Me 2—C≡C—(CH₂)₂O-(3-PrS-cHx) H H 1-879 H H H Me 2 —C≡C—(CH₂)₂O-(4-PrS-cHx) HH 1-880 H H H Me 2 —C≡C—(CH₂)₂O-(3-iPrS-cHx) H H 1-881 H H H Me 2—C≡C—(CH₂)₂O-(4-iPrS-cHx) H H 1-882 H H H Me 2—C≡C—(CH₂)₂O-[3-(2-Et-PrS)-cHx] H H 1-883 H H H Me 2—C≡C—(CH₂)₂O-[4-(2-Et-PrS)-cHx] H H 1-884 H H H Me 2—C≡C—(CH₂)₂O-(3-iBuS-cHx) H H 1-885 H H H Me 2 —C≡C—(CH₂)₂O-(4-iBuS-cHx)H H 1-886 H H H Me 2 —C≡C—(CH₂)₂O-(3-cHx-cHx) H H 1-887 H H H Me 2—C≡C—(CH₂)₂O-(4-cHx-cHx) H H 1-888 H H H Me 2 —C≡C—(CH₂)₂O-(3-Ph-cHx) HH 1-889 H H H Me 2 —C≡C—(CH₂)₂O-(4-Ph-cHx) H H 1-890 H H H Me 2—C≡C—(CH₂)₂O-(2,4-diMe-cHx) H H 1-891 H H H Me 2—C≡C—(CH₂)₂O-(3,4-diMe-cHx) H H 1-892 H H H Me 2—C≡C—(CH₂)₂O-(3,5-diMe-cHx) H H 1-893 H H H Me 2 —C≡C—(CH₂)₂O-Ph H H1-894 H H H Me 2 —C≡C—(CH₂)₂O-Ph Me H 1-895 H H H Me 2 —C≡C—(CH₂)₂O-Ph HMe 1-896 H H H Me 2 —C≡C—(CH₂)₂O-Ph F H 1-897 H H H Me 2 —C≡C—(CH₂)₂O-PhH F 1-898 H H H Me 2 —C≡C—(CH₂)₂O-(3-F-Ph) H H 1-899 H H H Me 2—C≡C—(CH₂)₂O-(4-F-Ph) H H 1-900 H H H Me 2 —C≡C—(CH₂)₂O-(4-Cl-Ph) H H1-901 H H H Me 2 —C≡C—(CH₂)₂O-(4-Br-Ph) H H 1-902 H H H Me 2—C≡C—(CH₂)₂O-(3-Me-Ph) H H 1-903 H H H Me 2 —C≡C—(CH₂)₂O-(4-Me-Ph) H H1-904 H H H Me 2 —C≡C—(CH₂)₂O-(3-Et-Ph) H H 1-905 H H H Me 2—C≡C—(CH₂)₂O-(4-Et-Ph) H H 1-906 H H H Me 2 —C≡C—(CH₂)₂O-(3-Pr-Ph) H H1-907 H H H Me 2 —C≡C—(CH₂)₂O-(4-Pr-Ph) H H 1-908 H H H Me 2—C≡C—(CH₂)₂O-(3-iPr-Ph) H H 1-909 H H H Me 2 —C≡C—(CH₂)₂O-(4-iPr-Ph) H H1-910 H H H Me 2 —C≡C—(CH₂)₂O-(3-Bu-Ph) H H 1-911 H H H Me 2—C≡C—(CH₂)₂O-(4-Bu-Ph) H H 1-912 H H H Me 2 —C≡C—(CH₂)₂O-(3-CF₃-Ph) H H1-913 H H H Me 2 —C≡C—(CH₂)₂O-(4-CF₃-Ph) H H 1-914 H H H Me 2—C≡C—(CH₂)₂O-(3-MeO-Ph) H H 1-915 H H H Me 2 —C≡C—(CH₂)₂O-(4-MeO-Ph) H H1-916 H H H Me 2 —C≡C—(CH₂)₂O-(3-EtO-Ph) H H 1-917 H H H Me 2—C≡C—(CH₂)₂O-(4-EtO-Ph) H H 1-918 H H H Me 2 —C≡C—(CH₂)₂O-(3-PrO-Ph) H H1-919 H H H Me 2 —C≡C—(CH₂)₂O-(4-PrO-Ph) H H 1-920 H H H Me 2—C≡C—(CH₂)₂O-(3-iPrO-Ph) H H 1-921 H H H Me 2 —C≡C—(CH₂)₂O-(4-iPrO-Ph) HH 1-922 H H H Me 2 —C≡C—(CH₂)₂O-[3-(2-Et-PrO)-Ph] H H 1-923 H H H Me 2—C≡C—(CH₂)₂O-[4-(2-Et-PrO)-Ph] H H 1-924 H H H Me 2—C≡C—(CH₂)₂O-(3-iBuO-Ph) H H 1-925 H H H Me 2 —C≡C—(CH₂)₂O-(4-iBuO-Ph) HH 1-926 H H H Me 2 —C≡C—(CH₂)₂O-(3-MeS-Ph) H H 1-927 H H H Me 2—C≡C—(CH₂)₂O-(4-MeS-Ph) H H 1-928 H H H Me 2 —C≡C—(CH₂)₂O-(3-EtS-Ph) H H1-929 H H H Me 2 —C≡C—(CH₂)₂O-(4-EtS-Ph) H H 1-930 H H H Me 2—C≡C—(CH₂)₂O-(3-PrS-Ph) H H 1-931 H H H Me 2 —C≡C—(CH₂)₂O-(4-PrS-Ph) H H1-932 H H H Me 2 —C≡C—(CH₂)₂O-(3-iPrS-Ph) H H 1-933 H H H Me 2—C≡C—(CH₂)₂O-(4-iPrS-Ph) H H 1-934 H H H Me 2—C≡C—(CH₂)₂O-[3-(2-Et-PrS)-Ph] H H 1-935 H H H Me 2—C≡C—(CH₂)₂O-[4-(2-Et-PrS)-Ph] H H 1-936 H H H Me 2—C≡C—(CH₂)₂O-(3-iBuS-Ph) H H 1-937 H H H Me 2 —C≡C—(CH₂)₂O-(4-iBuS-Ph) HH 1-938 H H H Me 2 —C≡C—(CH₂)₂O-(3-cHx-Ph) H H 1-939 H H H Me 2—C≡C—(CH₂)₂O-(4-cHx-Ph) H H 1-940 H H H Me 2 —C≡C—(CH₂)₂O-(3-Ph-Ph) H H1-941 H H H Me 2 —C≡C—(CH₂)₂O-(4-Ph-Ph) H H 1-942 H H H Me 2—C≡C—(CH₂)₂O-(2,4-diMe-Ph) H H 1-943 H H H Me 2—C≡C—(CH₂)₂O-(3,4-diMe-Ph) H H 1-944 H H H Me 2—C≡C—(CH₂)₂O-(3,5-diMe-Ph) H H 1-945 H H H Me 2 —C≡C—(CH₂)₃O-cHx H H1-946 H H H Me 2 —C≡C—(CH₂)₃O-Ph H H 1-947 H H H Me 2 —C≡C—(CH₂)₄O-cHx HH 1-948 H H H Me 2 —C≡C—(CH₂)₄O-Ph H H 1-949 H H H Me 2—C≡C—CH₂—OCH₂-cHx H H 1-950 H H H Me 2 —C≡C—CH₂—OCH₂-(4-F-cHx) H H 1-951H H H Me 2 —C≡C—CH₂—OCH₂-(4-Me-cHx) H H 1-952 H H H Me 2—C≡C—CH₂—OCH₂-(4-Et-cHx) H H 1-953 H H H Me 2 —C≡C—CH₂—OCH₂-(4-CF₃-cHx)H H 1-954 H H H Me 2 —C≡C—CH₂—OCH₂-(4-MeO-cHx) H H 1-955 H H H Me 2—C≡C—CH₂—OCH₂-(4-EtO-cHx) H H 1-956 H H H Me 2 —C≡C—CH₂—OCH₂-(4-MeS-cHx)H H 1-957 H H H Me 2 —C≡C—CH₂—OCH₂-(4-cHx-cHx) H H 1-958 H H H Me 2—C≡C—CH₂—OCH₂-(4-Ph-cHx) H H 1-959 H H H Me 2 —C≡C—CH₂—OCH₂-Ph H H 1-960H H H Me 2 —C≡C—CH₂—OCH₂-(4-F-Ph) H H 1-961 H H H Me 2—C≡C—CH₂—OCH₂-(4-Me-Ph) H H 1-962 H H H Me 2 —C≡C—CH₂—OCH₂-(4-Et-Ph) H H1-963 H H H Me 2 —C≡C—CH₂—OCH₂-(4-CF₃-Ph) H H 1-964 H H H Me 2—C≡C—CH₂—OCH₂-(4-MeO-Ph) H H 1-965 H H H Me 2 —C≡C—CH₂—OCH₂-(4-EtO-Ph) HH 1-966 H H H Me 2 —C≡C—CH₂—OCH₂-(4-MeS-Ph) H H 1-967 H H H Me 2—C≡C—CH₂—OCH₂-(4-cHx-Ph) H H 1-968 H H H Me 2 —C≡C—CH₂—OCH₂-(4-Ph-Ph) HH 1-969 H H H Me 2 —C≡C—(CH₂)₂—OCH₂-cPn H H 1-970 H H H Me 2—C≡C—(CH₂)₂—OCH₂-cHx H H 1-971 H H H Me 2 —C≡C—(CH₂)₂—OCH₂-cHx Me H1-972 H H H Me 2 —C≡C—(CH₂)₂—OCH₂-cHx H Me 1-973 H H H Me 2—C≡C—(CH₂)₂—OCH₂-cHx F H 1-974 H H H Me 2 —C≡C—(CH₂)₂—OCH₂-cHx H F 1-975H H H Me 2 —C≡C—(CH₂)₂—OCH₂-(3-F-cHx) H H 1-976 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-F-cHx) H H 1-977 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Cl-cHx) H H 1-978 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Br-cHx) H H 1-979 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-Me-cHx) H H 1-980 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Me-cHx) H H 1-981 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-Et-cHx) H H 1-982 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Et-cHx) H H 1-983 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-Pr-cHx) H H 1-984 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Pr-cHx) H H 1-985 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-iPr-cHx) H H 1-986 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-Bu-cHx) H H 1-987 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Bu-cHx) H H 1-988 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-CF₃-cHx) H H 1-989 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-CF₃-cHx) H H 1-990 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-MeO-cHx) H H 1-991 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-MeO-cHx) H H 1-992 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-EtO-cHx) H H 1-993 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-EtO-cHx) H H 1-994 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-PrO-cHx) H H 1-995 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-PrO-cHx) H H 1-996 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-iPrO-cHx) H H 1-997 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-iPrO-cHx) H H 1-998 H H H Me 2—C≡C—(CH₂)₂—OCH₂-[3-(2-Et-PrO)cHx] H H 1-999 H H H Me 2—C≡C—(CH₂)₂—OCH₂-[4-(2-Et-PrO)cHx] H H 1-1000 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-iBuO-cHx) H H 1-1001 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-iBuO-cHx) H H 1-1002 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-MeS-cHx) H H 1-1003 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-MeS-cHx) H H 1-1004 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-EtS-cHx) H H 1-1005 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-EtS-cHx) H H 1-1006 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-PrS-cHx) H H 1-1007 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-PrS-cHx) H H 1-1008 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-iPrS-cHx) H H 1-1009 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-iPrS-cHx) H H 1-1010 H H H Me 2—C≡C—(CH₂)₂—OCH₂-[3-(2-Et-PrS)cHx] H H 1-1011 H H H Me 2—C≡C—(CH₂)₂—OCH₂-[4-(2-Et-PrS)cHx] H H 1-1012 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-iBuS-cHx) H H 1-1013 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-iBuS-cHx) H H 1-1014 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-cHx-cHx) H H 1-1015 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-cHx-cHx) H H 1-1016 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-Ph-cHx) H H 1-1017 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Ph-cHx) H H 1-1018 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(2,4-diMe-cHx) H H 1-1019 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3,4-diMe-cHx) H H 1-1020 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3,5-diMe-cHx) H H 1-1021 H H H Me 2—C≡C—(CH₂)₂—OCH₂-Ph H H 1-1022 H H H Me 2 —C≡C—(CH₂)₂—OCH₂-Ph Me H1-1023 H H H Me 2 —C≡C—(CH₂)₂—OCH₂-Ph H Me 1-1024 H H H Me 2—C≡C—(CH₂)₂—OCH₂-Ph F H 1-1025 H H H Me 2 —C≡C—(CH₂)₂—OCH₂-Ph H F 1-1026H H H Me 2 —C≡C—(CH₂)₂—OCH₂-(3-F-Ph) H H 1-1027 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-F-Ph) H H 1-1028 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Cl-Ph) H H 1-1029 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Br-Ph) H H 1-1030 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-Me-Ph) H H 1-1031 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Me-Ph) H H 1-1032 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-Et-Ph) H H 1-1033 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Et-Ph) H H 1-1034 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-Pr-Ph) H H 1-1035 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Pr-Ph) H H 1-1036 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-iPr-Ph) H H 1-1037 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-iPr-Ph) H H 1-1038 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-Bu-Ph) H H 1-1039 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Bu-Ph) H H 1-1040 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-CF₃-Ph) H H 1-1041 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-CF₃-Ph) H H 1-1042 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-MeO-Ph) H H 1-1043 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-MeO-Ph) H H 1-1044 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-EtO-Ph) H H 1-1045 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-EtO-Ph) H H 1-1046 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-PrO-Ph) H H 1-1047 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-PrO-Ph) H H 1-1048 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-iPrO-Ph) H H 1-1049 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-iPrO-Ph) H H 1-1050 H H H Me 2—C≡C—(CH₂)₂—OCH₂-[3-(2-Et-PrO)Ph] H H 1-1051 H H H Me 2—C≡C—(CH₂)₂—OCH₂-[4-(2-Et-PrO)Ph] H H 1-1052 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-iBuO-Ph) H H 1-1053 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-iBuO-Ph) H H 1-1054 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-MeS-Ph) H H 1-1055 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-MeS-Ph) H H 1-1056 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-EtS-Ph) H H 1-1057 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-EtS-Ph) H H 1-1058 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-PrS-Ph) H H 1-1059 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-PrS-Ph) H H 1-1060 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-iPrS-Ph) H H 1-1061 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-iPrS-Ph) H H 1-1062 H H H Me 2—C≡C—(CH₂)₂—OCH₂-[3-(2-Et-PrS)Ph] H H 1-1063 H H H Me 2—C≡C—(CH₂)₂—OCH₂-[4-(2-Et-PrS)Ph] H H 1-1064 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-iBuS-Ph) H H 1-1065 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-iBuS-Ph) H H 1-1066 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-cHx-Ph) H H 1-1067 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-cHx-Ph) H H 1-1068 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-Ph-Ph) H H 1-1069 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Ph-Ph) H H 1-1070 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(2,4-diMe-Ph) H H 1-1071 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3,4-diMe-Ph) H H 1-1072 H H H Me 2—C≡C—(CH₂)₂—OCH₂-(3,5-diMe-Ph) H H 1-1073 H H H Me 2—C≡C—(CH₂)₃—OCH₂-cHx H H 1-1074 H H H Me 2 —C≡C—(CH₂)₃—OCH₂-Ph H H1-1075 H H H Me 2 —C≡C—(CH₂)₄—OCH₂-cHx H H 1-1076 H H H Me 2—C≡C—(CH₂)₄—OCH₂-Ph H H 1-1077 H H H Me 2 —CO—CH₂-(4-cHx-Ph) H H 1-1078H H H Me 2 —CO—CH₂-(4-Ph-Ph) H H 1-1079 H H H Me 2 —CO—(CH₂)₂-cHx H H1-1080 H H H Me 2 —CO—(CH₂)₂-Ph H H 1-1081 H H H Me 2 —CO—(CH₂)₃-cHx H H1-1082 H H H Me 2 —CO—(CH₂)₃-Ph H H 1-1083 H H H Me 2 —CO—(CH₂)₄-cHx H H1-1084 H H H Me 2 —CO—(CH₂)₄-(4-F-cHx) H H 1-1085 H H H Me 2—CO—(CH₂)₄-(4-Me-cHx) H H 1-1086 H H H Me 2 —CO—(CH₂)₄-(4-Et-cHx) H H1-1087 H H H Me 2 —CO—(CH₂)₄-(4-CF₃-cHx) H H 1-1088 H H H Me 2—CO—(CH₂)₄-(4-MeO-cHx) H H 1-1089 H H H Me 2 —CO—(CH₂)₄-(4-EtO-cHx) H H1-1090 H H H Me 2 —CO—(CH₂)₄-(4-MeS-cHx) H H 1-1091 H H H Me 2—CO—(CH₂)₄-(4-cHx-cHx) H H 1-1092 H H H Me 2 —CO—(CH₂)₄-(4-Ph-cHx) H H1-1093 H H H Me 2 —CO—(CH₂)₄-Ph H H 1-1094 H H H Me 2—CO—(CH₂)₄-(4-F-Ph) H H 1-1095 H H H Me 2 —CO—(CH₂)₄-(4-Me-Ph) H H1-1096 H H H Me 2 —CO—(CH₂)₄-(4-Et-Ph) H H 1-1097 H H H Me 2—CO—(CH₂)₄-(4-CF₃-Ph) H H 1-1098 H H H Me 2 —CO—(CH₂)₄-(4-MeO-Ph) H H1-1099 H H H Me 2 —CO—(CH₂)₄-(4-EtO-Ph) H H 1-1100 H H H Me 2—CO—(CH₂)₄-(4-MeS-Ph) H H 1-1101 H H H Me 2 —CO—(CH₂)₄-(4-cHx-Ph) H H1-1102 H H H Me 2 —CO—(CH₂)₄-(4-Ph-Ph) H H 1-1103 H H H Me 2—CO—(CH₂)₅-cHx H H 1-1104 H H H Me 2 —CO—(CH₂)₅-(4-F-cHx) H H 1-1105 HH. H Me 2 —CO—(CH₂)₅-(4-Me-cHx) H H 1-1106 H H H Me 2—CO—(CH₂)₅-(4-Et-cHx) H H 1-1107 H H H Me 2 —CO—(CH₂)₅-(4-CF₃-cHx) H H1-1108 H H H Me 2 —CO—(CH₂)₅-(4-MeO-cHx) H H 1-1109 H H H Me 2—CO—(CH₂)₅-(4-EtO-cHx) H H 1-1110 H H H Me 2 —CO—(CH₂)₅-(4-MeS-cHx) H H1-1111 H H H Me 2 —CO—(CH₂)₅-(4-cHx-cHx) H H 1-1112 H H H Me 2—CO—(CH₂)₅-(4-Ph-cHx) H H 1-1113 H H H Me 2 —CO—(CH₂)₅-Ph H H 1-1114 H HH Me 2 —CO—(CH₂)₅-(4-F-Ph) H H 1-1115 H H H Me 2 —CO—(CH₂)₅-(4-Me-Ph) HH 1-1116 H H H Me 2 —CO—(CH₂)₅-(4-Et-Ph) H H 1-1117 H H H Me 2—CO—(CH₂)₅-(4-CF₃-Ph) H H 1-1118 H H H Me 2 —CO—(CH₂)₅-(4-MeO-Ph) H H1-1119 H H H Me 2 —CO—(CH₂)₅-(4-EtO-Ph) H H 1-1120 H H H Me 2—CO—(CH₂)₅-(4-MeS-Ph) H H 1-1121 H H H Me 2 —CO—(CH₂)₅-(4-cHx-Ph) H H1-1122 H H H Me 2 —CO—(CH₂)₅-(4-Ph-Ph) H H 1-1123 H H H Me 2—CO—(CH₂)₆-cHx H H 1-1124 H H H Me 2 —CO—(CH₂)₆-Ph H H 1-1125 H H H Me 2—CO—(CH₂)₇-cHx H H 1-1126 H H H Me 2 —CO—(CH₂)₇-Ph H H 1-1127 H H H Me 2—CO—(CH₂)₂—O-cHx H H 1-1128 H H H Me 2 —CO—(CH₂)₂—O-(4-F-cHx) H H 1-1129H H H Me 2 —CO—(CH₂)₂—O-(4-Me-cHx) H H 1-1130 H H H Me 2—CO—(CH₂)₂—O-(4-Et-cHx) H H 1-1131 H H H Me 2 —CO—(CH₂)₂—O-(4-CF₃-cHx) HH 1-1132 H H H Me 2 —CO—(CH₂)₂—O-(4-MeO-cHx) H H 1-1133 H H H Me 2—CO—(CH₂)₂—O-(4-EtO-cHx) H H 1-1134 H H H Me 2 —CO—(CH₂)₂—O-(4-MeS-cHx)H H 1-1135 H H H Me 2 —CO—(CH₂)₂—O-(4-cHx-cHx) H H 1-1136 H H H Me 2—CO—(CH₂)₂—O-(4-Ph-cHx) H H 1-1137 H H H Me 2 —CO—(CH₂)₂—O-Ph H H 1-1138H H H Me 2 —CO—(CH₂)₂—O-(4-F-Ph) H H 1-1139 H H H Me 2—CO—(CH₂)₂—O-(4-Me-Ph) H H 1-1140 H H H Me 2 —CO—(CH₂)₂—O-(4-Et-Ph) H H1-1141 H H H Me 2 —CO—(CH₂)₂—O-(4-CF₃-Ph) H H 1-1142 H H H Me 2—CO—(CH₂)₂—O-(4-MeO-Ph) H H 1-1143 H H H Me 2 —CO—(CH₂)₂—O-(4-EtO-Ph) HH 1-1144 H H H Me 2 —CO—(CH₂)₂—O-(4-MeS-Ph) H H 1-1145 H H H Me 2—CO—(CH₂)₂—O-(4-cHx-Ph) H H 1-1146 H H H Me 2 —CO—(CH₂)₂—O-(4-Ph-Ph) H H1-1147 H H H Me 2 —CO—(CH₂)₃—O-cPn H H 1-1148 H H H Me 2—CO—(CH₂)₃—O-cHx H H 1-1149 H H H Me 2 —CO—(CH₂)₃—O-cHx Me H 1-1150 H HH Me 2 —CO—(CH₂)₃—O-cHx H Me 1-1151 H H H Me 2 —CO—(CH₂)₃—O-cHx F H1-1152 H H H Me 2 —CO—(CH₂)₃—O-cHx H F 1-1153 H H H Me 2—CO—(CH₂)₃—O-(3-F-cHx) H H 1-1154 H H H Me 2 —CO—(CH₂)₃—O-(4-F-cHx) H H1-1155 H H H Me 2 —CO—(CH₂)₃—O-(4-Cl-cHx) H H 1-1156 H H H Me 2—CO—(CH₂)₃—O-(4-Br-cHx) H H 1-1157 H H H Me 2 —CO—(CH₂)₃—O-(3-Me-cHx) HH 1-1158 H H H Me 2 —CO—(CH₂)₃—O-(4-Me-cHx) H H 1-1159 H H H Me 2—CO—(CH₂)₃—O-(3-Et-cHx) H H 1-1160 H H H Me 2 —CO—(CH₂)₃—O-(4-Et-cHx) HH 1-1161 H H H Me 2 —CO—(CH₂)₃—O-(3-Pr-cHx) H H 1-1162 H H H Me 2—CO—(CH₂)₃—O-(4-Pr-cHx) H H 1-1163 H H H Me 2 —CO—(CH₂)₃—O-(4-iPr-cHx) HH 1-1164 H H H Me 2 —CO—(CH₂)₃—O-(3-Bu-cHx) H H 1-1165 H H H Me 2—CO—(CH₂)₃—O-(4-Bu-cHx) H H 1-1166 H H H Me 2 —CO—(CH₂)₃—O-(3-CF₃-cHx) HH 1-1167 H H H Me 2 —CO—(CH₂)₃—O-(4-CF₃-cHx) H H 1-1168 H H H Me 2—CO—(CH₂)₃—O-(3-MeO-cHx) H H 1-1169 H H H Me 2 —CO—(CH₂)₃—O-(4-MeO-cHx)H H 1-1170 H H H Me 2 —CO—(CH₂)₃—O-(3-EtO-cHx) H H 1-1171 H H H Me 2—CO—(CH₂)₃—O-(4-EtO-cHx) H H 1-1172 H H H Me 2 —CO—(CH₂)₃—O-(3-PrO-cHx)H H 1-1173 H H H Me 2 —CO—(CH₂)₃—O-(4-PrO-cHx) H H 1-1174 H H H Me 2—CO—(CH₂)₃—O-(3-iPrO-cHx) H H 1-1175 H H H Me 2—CO—(CH₂)₃—O-(4-iPrO-cHx) H H 1-1176 H H H Me 2—CO—(CH₂)₃—O-[3-(2-Et-PrO)cHx] H H 1-1177 H H H Me 2—CO—(CH₂)₃—O-[4-(2-Et-PrO)cHx] H H 1-1178 H H H Me 2—CO—(CH₂)₃—O-(3-iBuO-cHx) H H 1-1179 H H H Me 2—CO—(CH₂)₃—O-(4-iBuO-cHx) H H 1-1180 H H H Me 2 —CO—(CH₂)₃—O-(3-MeS-cHx)H H 1-1181 H H H Me 2 —CO—(CH₂)₃—O-(4-MeS-cHx) H H 1-1182 H H H Me 2—CO—(CH₂)₃—O-(3-EtS-cHx) H H 1-1183 H H H Me 2 —CO—(CH₂)₃—O-(4-EtS-cHx)H H 1-1184 H H H Me 2 —CO—(CH₂)₃—O-(3-PrS-cHx) H H 1-1185 H H H Me 2—CO—(CH₂)₃—O-(4-PrS-cHx) H H 1-1186 H H H Me 2 —CO—(CH₂)₃—O-(3-iPrS-cHx)H H 1-1187 H H H Me 2 —CO—(CH₂)₃—O-(4-iPrS-cHx) H H 1-1188 H H H Me 2—CO—(CH₂)₃—O-[3-(2-Et-PrS)cHx] H H 1-1189 H H H Me 2—CO—(CH₂)₃—O-[4-(2-Et-PrS)cHx] H H 1-1190 H H H Me 2—CO—(CH₂)₃—O-(3-iBuS-cHx) H H 1-1191 H H H Me 2—CO—(CH₂)₃—O-(4-iBuS-cHx) H H 1-1192 H H H Me 2 —CO—(CH₂)₃—O-(3-cHx-cHx)H H 1-1193 H H H Me 2 —CO—(CH₂)₃—O-(4-cHx-cHx) H H 1-1194 H H H Me 2—CO—(CH₂)₃—O-(3-Ph-cHx) H H 1-1195 H H H Me 2 —CO—(CH₂)₃—O-(4-Ph-cHx) HH 1-1196 H H H Me 2 —CO—(CH₂)₃—O-(2,4-diMe-cHx) H H 1-1197 H H H Me 2—CO—(CH₂)₃—O-(3,4-diMe-cHx) H H 1-1198 H H H Me 2—CO—(CH₂)₃—O-(3,5-diMe-cHx) H H 1-1199 H H H Me 2 —CO—(CH₂)₃—O-Ph H H1-1200 H H H Me 2 —CO—(CH₂)₃—O-Ph Me H 1-1201 H H H Me 2 —CO—(CH₂)₃—O-PhH Me 1-1202 H H H Me 2 —CO—(CH₂)₃—O-Ph F H 1-1203 H H H Me 2—CO—(CH₂)₃—O-Ph H F 1-1204 H H H Me 2 —CO—(CH₂)₃—O-(3-F-Ph) H H 1-1205 HH H Me 2 —CO—(CH₂)₃—O-(4-F-Ph) H H 1-1206 H H H Me 2—CO—(CH₂)₃—O-(4-Cl-Ph) H H 1-1207 H H H Me 2 —CO—(CH₂)₃—O-(4-Br-Ph) H H1-1208 H H H Me 2 —CO—(CH₂)₃—O-(3-Me-Ph) H H 1-1209 H H H Me 2—CO—(CH₂)₃—O-(4-Me-Ph) H H 1-1210 H H H Me 2 —CO—(CH₂)₃—O-(3-Et-Ph) H H1-1211 H H H Me 2 —CO—(CH₂)₃—O-(4-Et-Ph) H H 1-1212 H H H Me 2—CO—(CH₂)₃—O-(3-Pr-Ph) H H 1-1213 H H H Me 2 —CO—(CH₂)₃—O-(4-Pr-Ph) H H1-1214 H H H Me 2 —CO—(CH₂)₃—O-(3-iPr-Ph) H H 1-1215 H H H Me 2—CO—(CH₂)₃—O-(4-iPr-Ph) H H 1-1216 H H H Me 2 —CO—(CH₂)₃—O-(3-Bu-Ph) H H1-1217 H H H Me 2 —CO—(CH₂)₃—O-(4-Bu-Ph) H H 1-1218 H H H Me 2—CO—(CH₂)₃—O-(3-CF₃-Ph) H H 1-1219 H H H Me 2 —CO—(CH₂)₃—O-(4-CF₃-Ph) HH 1-1220 H H H Me 2 —CO—(CH₂)₃—O-(3-MeO-Ph) H H 1-1221 H H H Me 2—CO—(CH₂)₃—O-(4-MeO-Ph) H H 1-1222 H H H Me 2 —CO—(CH₂)₃—O-(3-EtO-Ph) HH 1-1223 H H H Me 2 —CO—(CH₂)₃—O-(4-EtO-Ph) H H 1-1224 H H H Me 2—CO—(CH₂)₃—O-(3-PrO-Ph) H H 1-1225 H H H Me 2 —CO—(CH₂)₃—O-(4-PrO-Ph) HH 1-1226 H H H Me 2 —CO—(CH₂)₃—O-(3-iPrO-Ph) H H 1-1227 H H H Me 2—CO—(CH₂)₃—O-(4-iPrO-Ph) H H 1-1228 H H H Me 2—CO—(CH₂)₃—O-[3-(2-Et-PrO)-Ph) H H 1-1229 H H H Me 2—CO—(CH₂)₃—O-[4-(2-Et-PrO)-PhJ H H 1-1230 H H H Me 2—CO—(CH₂)₃—O-(3-iBuO-Ph) H H 1-1231 H H H Me 2 —CO—(CH₂)₃—O-(4-iBuO-Ph)H H 1-1232 H H H Me 2 —CO—(CH₂)₃—O-(3-MeS-Ph) H H 1-1233 H H H Me 2—CO—(CH₂)₃—O-(4-MeS-Ph) H H 1-1234 H H H Me 2 —CO—(CH₂)₃—O-(3-EtS-Ph) HH 1-1235 H H H Me 2 —CO—(CH₂)₃—O-(4-EtS-Ph) H H 1-1236 H H H Me 2—CO—(CH₂)₃—O-(3-PrS-Ph) H H 1-1237 H H H Me 2 —CO—(CH₂)₃—O-(4-PrS-Ph) HH 1-1238 H H H Me 2 —CO—(CH₂)₃—O-(3-iPrS-Ph) H H 1-1239 H H H Me 2—CO—(CH₂)₃—O-(4-iPrS-Ph) H H 1-1240 H H H Me 2—CO—(CH₂)₃—O-[3-(2-Et-PrS)-Ph] H H 1-1241 H H H Me 2—CO—(CH₂)₃—O-[4-(2-Et-PrS)-Ph] H H 1-1242 H H H Me 2—CO—(CH₂)₃—O-(3-iBuS-Ph) H H 1-1243 H H H Me 2 —CO—(CH₂)₃—O-(4-iBuS-Ph)H H 1-1244 H H H Me 2 —CO—(CH₂)₃—O-(3-cHx-Ph) H H 1-1245 H H H Me 2—CO—(CH₂)₃—O-(4-cHx-Ph) H H 1-1246 H H H Me 2 —CO—(CH₂)₃—O-(3-Ph-Ph) H H1-1247 H H H Me 2 —CO—(CH₂)₃—O-(4-Ph-Ph) H H 1-1248 H H H Me 2—CO—(CH₂)₃—O-(2,4-diMe-Ph) H H 1-1249 H H H Me 2—CO—(CH₂)₃—O-(3,4-diMe-Ph) H H 1-1250 H H H Me 2—CO—(CH₂)₃—O-(3,5-diMe-Ph) H H 1-1251 H H H Me 2 —CO—(CH₂)₄—O-cHx H H1-1252 H H H Me 2 —CO—(CH₂)₄—O-Ph H H 1-1253 H H H Me 2 —CO—(CH₂)₅—O-cHxH H 1-1254 H H H Me 2 —CO—(CH₂)₅—O-Ph H H 1-1255 H H H Me 2—CO—(CH₂)₂—OCH₂-cHx H H 1-1256 H H H Me 2 —CO—(CH₂)₂—OCH₂-(4-F-cHx) H H1-1257 H H H Me 2 —CO—(CH₂)₂—OCH₂-(4-Me-cHx) H H 1-1258 H H H Me 2—CO—(CH₂)₂—OCH₂-(4-Et-cHx) H H 1-1259 H H H Me 2—CO—(CH₂)₂—OCH₂-(4-CF₃-cHx) H H 1-1260 H H H Me 2—CO—(CH₂)₂—OCH₂-(4-MeO-cHx) H H 1-1261 H H H Me 2—CO—(CH₂)₂—OCH₂-(4-EtO-cHx) H H 1-1262 H H H Me 2—CO—(CH₂)₂—OCH₂-(4-MeS-cHx) H H 1-1263 H H H Me 2—CO—(CH₂)₂—OCH₂-(4-cHx-cHx) H H 1-1264 H H H Me 2—CO—(CH₂)₂—OCH₂-(4-Ph-cHx) H H 1-1265 H H H Me 2 —CO—(CH₂)₂—OCH₂-Ph H H1-1266 H H H Me 2 —CO—(CH₂)₂—OCH₂-(4-F-Ph) H H 1-1267 H H H Me 2—CO—(CH₂)₂—OCH₂-(4-Me-Ph) H H 1-1268 H H H Me 2—CO—(CH₂)₂—OCH₂-(4-Et-Ph) H H 1-1269 H H H Me 2—CO—(CH₂)₂—OCH₂-(4-CF₃-Ph) H H 1-1270 H H H Me 2—CO—(CH₂)₂—OCH₂-(4-MeO-Ph) H H 1-1271 H H H Me 2—CO—(CH₂)₂—OCH₂-(4-EtO-Ph) H H 1-1272 H H H Me 2—CO—(CH₂)₂—OCH₂-(4-MeS-Ph) H H 1-1273 H H H Me 2—CO—(CH₂)₂—OCH₂-(4-cHx-Ph) H H 1-1274 H H H Me 2—CO—(CH₂)₂—OCH₂-(4-Ph-Ph) H H 1-1275 H H H Me 2 —CO—(CH₂)₃—OCH₂—CH₂-cPnH H 1-1276 H H H Me 2 —CO—(CH₂)₃—OCH₂-cHx H H 1-1277 H H H Me 2—CO—(CH₂)₃—OCH₂-cHx Me H 1-1278 H H H Me 2 —CO—(CH₂)₃—OCH₂-cHx H Me1-1279 H H H Me 2 —CO—(CH₂)₃—OCH₂-cHx F H 1-1280 H H H Me 2—CO—(CH₂)₃—OCH₂-cHx H F 1-1281 H H H Me 2 —CO—(CH₂)₃—OCH₂-(3-F-cHx) H H1-1282 H H H Me 2 —CO—(CH₂)₃—OCH₂-(4-F-cHx) H H 1-1283 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-Cl-cHx) H H 1-1284 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-Br-cHx) H H 1-1285 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-Me-cHx) H H 1-1286 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-Me-cHx) H H 1-1287 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-Et-cHx) H H 1-1288 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-Et-cHx) H H 1-1289 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-Pr-cHx) H H 1-1290 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-Pr-cHx) H H 1-1291 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-iPr-cHx) H H 1-1292 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-Bu-cHx) H H 1-1293 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-Bu-cHx) H H 1-1294 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-CF₃-cHx) H H 1-1295 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-CF₃-cHx) H H 1-1296 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-MeO-cHx) H H 1-1297 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-MeO-cHx) H H 1-1298 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-EtO-cHx) H H 1-1299 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-EtO-cHx) H H 1-1300 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-PrO-cHx) H H 1-1301 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-PrO-cHx) H H 1-1302 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-iPrO-cHx) H H 1-1303 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-iPrO-cHx) H H 1-1304 H H H Me 2—CO—(CH₂)₃—OCH₂-[3-(2-Et-PrO)cHx] H H 1-1305 H H H Me 2—CO—(CH₂)₃—OCH₂-[4-(2-Et-PrO)cHx] H H 1-1306 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-iBuO-cHx) H H 1-1307 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-iBuO-cHx) H H 1-1308 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-MeS-cHx) H H 1-1309 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-MeS-cHx) H H 1-1310 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-EtS-cHx) H H 1-1311 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-EtS-cHx) H H 1-1312 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-PrS-cHx) H H 1-1313 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-PrS-cHx) H H 1-1314 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-iPrS-cHx) H H 1-1315 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-iPrS-cHx) H H 1-1316 H H H Me 2—CO—(CH₂)₃—OCH₂-[3-(2-Et-PrS)cHx] H H 1-1317 H H H Me 2—CO—(CH₂)₃—OCH₂-[4-(2-Et-PrS)cHx] H H 1-1318 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-iBuS-cHx) H H 1-1319 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-iBuS-cHx) H H 1-1320 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-cHx-cHx) H H 1-1321 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-cHx-cHx) H H 1-1322 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-Ph-cHx) H H 1-1323 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-Ph-cHx) H H 1-1324 H H H Me 2—CO—(CH₂)₃—OCH₂-(2,4-diMe-cHx) H H 1-1325 H H H Me 2—CO—(CH₂)₃—OCH₂-(3,4-diMe-cHx) H H 1-1326 H H H Me 2—CO—(CH₂)₃—OCH₂-(3,5-diMe-cHx) H H 1-1327 H H H Me 2 —CO—(CH₂)₃—OCH₂-PhH H 1-1328 H H H Me 2 —CO—(CH₂)₃—OCH₂-Ph Me H 1-1329 H H H Me 2—CO—(CH₂)₃—OCH₂-Ph H Me 1-1330 H H H Me 2 —CO—(CH₂)₃—OCH₂-Ph F H 1-1331H H H Me 2 —CO—(CH₂)₃—OCH₂-Ph H F 1-1332 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-F-Ph) H H 1-1333 H H H Me 2 —CO—(CH₂)₃—OCH₂-(4-F-Ph)H H 1-1334 H H H Me 2 —CO—(CH₂)₃—OCH₂-(4-Cl-Ph) H H 1-1335 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-Br-Ph) H H 1-1336 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-Me-Ph) H H 1-1337 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-Me-Ph) H H 1-1338 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-Et-Ph) H H 1-1339 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-Et-Ph) H H 1-1340 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-Pr-Ph) H H 1-1341 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-Pr-Ph) H H 1-1342 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-iPr-Ph) H H 1-1343 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-iPr-Ph) H H 1-1344 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-Bu-Ph) H H 1-1345 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-Bu-Ph) H H 1-1346 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-CF₃-Ph) H H 1-1347 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-CF₃-Ph) H H 1-1348 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-MeO-Ph) H H 1-1349 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-MeO-Ph) H H 1-1350 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-EtO-Ph) H H 1-1351 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-EtO-Ph) H H 1-1352 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-PrO-Ph) H H 1-1353 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-PrO-Ph) H H 1-1354 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-iPrO-Ph) H H 1-1355 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-iPrO-Ph) H H 1-1356 H H H Me 2—CO—(CH₂)₃—OCH₂-[3-(2-Et-PrO)Ph] H H 1-1357 H H H Me 2—CO—(CH₂)₃—OCH₂-[4-(2-Et-PrO)Ph] H H 1-1358 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-iBuO-Ph) H H 1-1359 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-iBuO-Ph) H H 1-1360 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-MeS-Ph) H H 1-1361 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-MeS-Ph) H H 1-1362 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-EtS-Ph) H H 1-1363 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-EtS-Ph) H H 1-1364 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-PrS-Ph) H H 1-1365 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-PrS-Ph) H H 1-1366 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-iPrS-Ph) H H 1-1367 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-iPrS-Ph) H H 1-1368 H H H Me 2—CO—(CH₂)₃—OCH₂-[3-(2-Et-PrS)Ph] H H 1-1369 H H H Me 2—CO—(CH₂)₃—OCH₂-[4-(2-Et-PrS)Ph] H H 1-1370 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-iBuS-Ph) H H 1-1371 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-iBuS-Ph) H H 1-1372 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-cHx-Ph) H H 1-1373 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-cHx-Ph) H H 1-1374 H H H Me 2—CO—(CH₂)₃—OCH₂-(3-Ph-Ph) H H 1-1375 H H H Me 2—CO—(CH₂)₃—OCH₂-(4-Ph-Ph) H H 1-1376 H H H Me 2—CO—(CH₂)₃—OCH₂-(2,4-diMe-Ph) H H 1-1377 H H H Me 2—CO—(CH₂)₃—OCH₂-(3,4-diMe-Ph) H H 1-1378 H H H Me 2—CO—(CH₂)₃—OCH₂-(3,5-diMe-Ph) H H 1-1379 H H H Me 2 —CO—(CH₂)₄—OCH₂-cHxH H 1-1380 H H H Me 2 —CO—(CH₂)₄—OCH₂-Ph H H 1-1381 H H H Me 2—CO—(CH₂)₅—OCH₂-cHx H H 1-1382 H H H Me 2 —CO—(CH₂)₅—OCH₂-Ph H H 1-1383H H H Me 2 —CH(OH)—CH₂-cHx H H 1-1384 H H H Me 2 —CH(OH)—CH₂-Ph H H1-1385 H H H Me 2 —CH(OH)—(CH₂)₂-cHx H H 1-1386 H H H Me 2—CH(OH)—(CH₂)₂-Ph H H 1-1387 H H H Me 2 —CH(OH)—(CH₂)₃-cHx H H 1-1388 HH H Me 2 —CH(OH)—(CH₂)₃-Ph H H 1-1389 H H H Me 2 —CH(OH)—(CH₂)₄-cHx H H1-1390 H H H Me 2 —CH(OH)—(CH₂)₄-(4-F-cHx) H H 1-1391 H H H Me 2—CH(OH)—(CH₂)₄-(4-Me-cHx) H H 1-1392 H H H Me 2—CH(OH)—(CH₂)₄-(4-Et-cHx) H H 1-1393 H H H Me 2—CH(OH)—(CH₂)₄-(4-CF₃-cHx) H H 1-1394 H H H Me 2—CH(OH)—(CH₂)₄-(4-MeO-cHx) H H 1-1395 H H H Me 2—CH(OH)—(CH₂)₄-(4-EtO-cHx) H H 1-1396 H H H Me 2—CH(OH)—(CH₂)₄-(4-MeS-cHx) H H 1-1397 H H H Me 2—CH(OH)—(CH₂)₄-(4-cHx-cHx) H H 1-1398 H H H Me 2—CH(OH)—(CH₂)₄-(4-Ph-cHx) H H 1-1399 H H H Me 2 —CH(OH)—(CH₂)₄-Ph H H1-1400 H H H Me 2 —CH(OH)—(CH₂)₄-(4-F-Ph) H H 1-1401 H H H Me 2—CH(OH)—(CH₂)₄-(4-Me-Ph) H H 1-1402 H H H Me 2 —CH(OH)—(CH₂)₄-(4-Et-Ph)H H 1-1403 H H H Me 2 —CH(OH)—(CH₂)₄-(4-CF₃-Ph) H H 1-1404 H H H Me 2—CH(OH)—(CH₂)₄-(4-MeO-Ph) H H 1-1405 H H H Me 2—CH(OH)—(CH₂)₄-(4-EtO-Ph) H H 1-1406 H H H Me 2—CH(OH)—(CH₂)₄-(4-MeS-Ph) H H 1-1407 H H H Me 2—CH(OH)—(CH₂)₄-(4-cHx-Ph) H H 1-1408 H H H Me 2 —CH(OH)—(CH₂)₄-(4-Ph-Ph)H H 1-1409 H H H Me 2 —CH(OH)—(CH₂)₅-cHx H H 1-1410 H H H Me 2—CH(OH)—(CH₂)₅-(4-F-cHx) H H 1-1411 H H H Me 2 —CH(OH)—(CH₂)₅-(4-Me-cHx)H H 1-1412 H H H Me 2 —CH(OH)—(CH₂)₅-(4-Et-cHx) H H 1-1413 H H H Me 2—CH(OH)—(CH₂)₅-(4-CF₃-cHx) H H 1-1414 H H H Me 2—CH(OH)—(CH₂)₅-(4-MeO-cHx) H H 1-1415 H H H Me 2—CH(OH)—(CH₂)₅-(4-EtO-cHx) H H 1-1416 H H H Me 2—CH(OH)—(CH₂)₅-(4-MeS-cHx) H H 1-1417 H H H Me 2—CH(OH)—(CH₂)₅-(4-cHx-cHx) H H 1-1418 H H H Me 2—CH(OH)—(CH₂)₅-(4-Ph-cHx) H H 1-1419 H H H Me 2 —CH(OH)—(CH₂)₅-Ph H H1-1420 H H H Me 2 —CH(OH)—(CH₂)₅-(4-F-Ph) H H 1-1421 H H H Me 2—CH(OH)—(CH₂)₅-(4-Me-Ph) H H 1-1422 H H H Me 2 —CH(OH)—(CH₂)₅-(4-Et-Ph)H H 1-1423 H H H Me 2 —CH(OH)—(CH₂)₅-(4-CF₃-Ph) H H 1-1424 H H H Me 2—CH(OH)—(CH₂)₅-(4-MeO-Ph) H H 1-1425 H H H Me 2—CH(OH)—(CH₂)₅-(4-EtO-Ph) H H 1-1426 H H H Me 2—CH(OH)—(CH₂)₅-(4-MeS-Ph) H H 1-1427 H H H Me 2—CH(OH)—(CH₂)₅-(4-cHx-Ph) H H 1-1428 H H H Me 2 —CH(OH)—(CH₂)₅-(4-Ph-Ph)H H 1-1429 H H H Me 2 —CH(OH)—(CH₂)₆-cHx H H 1-1430 H H H Me 2—CH(OH)—(CH₂)₆-Ph H H 1-1431 H H H Me 2 —CH(OH)—(CH₂)₇-cHx H H 1-1432 HH H Me 2 —CH(OH)—(CH₂)₇-Ph H H 1-1433 H H H Me 2 -4-(cHx-CH₂O)Ph H H1-1434 H H H Me 2 -4-(cHx-CH₂O)-2-F-Ph H H 1-1435 H H H Me 2-4-(cHx-CH₂O)-3-F-Ph H H 1-1436 H H H Me 2 -4-(cHx-CH₂O)-2,3-diF-Ph H H1-1437 H H H Me 2 -4-(cHx-CH₂O)-2-Cl-Ph H H 1-1438 H H H Me 2-4-(cHx-CH₂O)-3-Cl-Ph H H 1-1439 H H H Me 2 -4-(cHx-CH₂O)-2,3-diCl-Ph HH 1-1440 H H H Me 2 -4-(cHx-CH₂O)-2-Me-Ph H H 1-1441 H H H Me 2-4-(cHx-CH₂O)-3-Me-Ph H H 1-1442 H H H Me 2 -4-(cHx-CH₂O)-2,3-diMe-Ph HH 1-1443 H H H Me 2 -4-[cHx-(CH₂)₂O]Ph H H 1-1444 H H H Me 2-3-[cHx-(CH₂)₂O]Ph H H 1-1445 H H H Me 2 -(4-BzO-Ph) H H 1-1446 H H H Me2 -(4-BzO-2-F-Ph) H H 1-1447 H H H Me 2 -(4-BzO-3-F-Ph) H H 1-1448 H H HMe 2 -(4-BzO-2,3-diF-Ph) H H 1-1449 H H H Me 2 -(4-BzO-2-Cl-Ph) H H1-1450 H H H Me 2 -(4-BzO-3-Cl-Ph) H H 1-1451 H H H Me 2-(4-BzO-2,3-diCl-Ph) H H 1-1452 H H H Me 2 -(4-BzO-2-Me-Ph) H H 1-1453 HH H Me 2 -(4-BzO-3-Me-Ph) H H 1-1454 H H H Me 2 -(4-BzO-2,3-diMe-Ph) H H1-1455 H H H Me 2 -4-[Ph-(CH₂)₂O]-Ph H H 1-1456 H H H Me 2-4-[Ph-(CH₂)₃O]-Ph H H 1-1457 H H H Et 2 —(CH₂)₃-cHx H H 1-1458 H H H Et2 —(CH₂)₃-Ph H H 1-1459 H H H Et 2 —(CH₂)₄-cHx H H 1-1460 H H H Et 2—(CH₂)₄-Ph H H 1-1461 H H H Et 2 —(CH₂)₅-cPn H H 1-1462 H H H Et 2—(CH₂)₅-cHx H H 1-1463 H H H Et 2 —(CH₂)₅-cHx Me H 1-1464 H H H Et 2—(CH₂)₅-cHx H Me 1-1465 H H H Et 2 —(CH₂)₅-cHx F H 1-1466 H H H Et 2—(CH₂)₅-cHx H F 1-1467 H H H Et 2 —(CH₂)₅-(4-F-cHx) H H 1-1468 H H H Et2 —(CH₂)₅-(4-Cl-cHx) H H 1-1469 H H H Et 2 —(CH₂)₅-(4-Br-cHx) H H 1-1470H H H Et 2 —(CH₂)₅-(4-Me-cHx) H H 1-1471 H H H Et 2 —(CH₂)₅-(4-Et-cHx) HH 1-1472 H H H Et 2 —(CH₂)₅-(4-Pr-cHx) H H 1-1473 H H H Et 2—(CH₂)₅-(4-iPr-cHx) H H 1-1474 H H H Et 2 —(CH₂)₅-(4-CF₃-cHx) H H 1-1475H H H Et 2 —(CH₂)₅-(4-MeO-cHx) H H 1-1476 H H H Et 2 —(CH₂)₅-(4-EtO-cHx)H H 1-1477 H H H Et 2 —(CH₂)₅-(4-PrO-cHx) H H 1-1478 H H H Et 2—(CH₂)₅-(4-iPrO-cHx) H H 1-1479 H H H Et 2 —(CH₂)₅-(3-MeS-cHx) H H1-1480 H H H Et 2 —(CH₂)₅-(4-MeS-cHx) H H 1-1481 H H H Et 2—(CH₂)₅-(2,4-diMe-cHx) H H 1-1482 H H H Et 2 —(CH₂)₅-(3,4-diMe-cHx) H H1-1483 H H H Et 2 —(CH₂)₅-(3,5-diMe-cHx) H H 1-1484 H H H Et 2—(CH₂)₅-Ph H H 1-1485 H H H Et 2 —(CH₂)₅-Ph Me H 1-1486 H H H Et 2—(CH₂)₅-Ph H Me 1-1487 H H H Et 2 —(CH₂)₅-Ph F H 1-1488 H H H Et 2—(CH₂)₅-Ph H F 1-1489 H H H Et 2 —(CH₂)₅-(4-F-Ph) H H 1-1490 H H H Et 2—(CH₂)₅-(4-Cl-Ph) H H 1-1491 H H H Et 2 —(CH₂)₅-(4-Br-Ph) H H 1-1492 H HH Et 2 —(CH₂)₅-(4-Me-Ph) H H 1-1493 H H H Et 2 —(CH₂)₅-(4-Et-Ph) H H1-1494 H H H Et 2 —(CH₂)₅-(4-Pr-Ph) H H 1-1495 H H H Et 2—(CH₂)₅-(4-iPr-Ph) H H 1-1496 H H H Et 2 —(CH₂)₅-(4-Bu-Ph) H H 1-1497 HH H Et 2 —(CH₂)₅-(4-CF₃-Ph) H H 1-1498 H H H Et 2 —(CH₂)₅-(4-MeO-Ph) H H1-1499 H H H Et 2 —(CH₂)₅-(4-EtO-Ph) H H 1-1500 H H H Et 2—(CH₂)₅-(4-PrO-Ph) H H 1-1501 H H H Et 2 —(CH₂)₅-(4-iPrO-Ph) H H 1-1502H H H Et 2 —(CH₂)₅-(3-MeS-Ph) H H 1-1503 H H H Et 2 —(CH₂)₅-(4-MeS-Ph) HH 1-1504 H H H Et 2 —(CH₂)₅-(2,4-diMe-Ph) H H 1-1505 H H H Et 2—(CH₂)₅-(3,4-diMe-Ph) H H 1-1506 H H H Et 2 —(CH₂)₅-(3,5-diMe-Ph) H H1-1507 H H H Et 2 —(CH₂)₆-cPn H H 1-1508 H H H Et 2 —(CH₂)₆-cHx H H1-1509 H H H Et 2 —(CH₂)₆-cHx Me H 1-1510 H H H Et 2 —(CH₂)₆-cHx H Me1-1511 H H H Et 2 —(CH₂)₆-cHx F H 1-1512 H H H Et 2 —(CH₂)₆-cHx H F1-1513 H H H Et 2 —(CH₂)₆-(4-F-cHx) H H 1-1514 H H H Et 2—(CH₂)₆-(4-Cl-cHx) H H 1-1515 H H H Et 2 —(CH₂)₆-(4-Br-cHx) H H 1-1516 HH H Et 2 —(CH₂)₆-(4-Me-cHx) H H 1-1517 H H H Et 2 —(CH₂)₆-(4-Et-cHx) H H1-1518 H H H Et 2 —(CH₂)₆-(4-Pr-cHx) H H 1-1519 H H H Et 2—(CH₂)₆-(4-iPr-cHx) H H 1-1520 H H H Et 2 —(CH₂)₆-(4-Bu-cHx) H H 1-1521H H H Et 2 —(CH₂)₆-(4-CF₃-cHx) H H 1-1522 H H H Et 2 —(CH₂)₆-(4-MeO-cHx)H H 1-1523 H H H Et 2 —(CH₂)₆-(4-EtO-cHx) H H 1-1524 H H H Et 2—(CH₂)₆-(4-PrO-cHx) H H 1-1525 H H H Et 2 —(CH₂)₆-(4-iPrO-cHx) H H1-1526 H H H Et 2 —(CH₂)₆-(3-MeS-cHx) H H 1-1527 H H H Et 2—(CH₂)₆-(4-MeS-cHx) H H 1-1528 H H H Et 2 —(CH₂)₆-(2,4-diMe-cHx) H H1-1529 H H H Et 2 —(CH₂)₆-(3,4-diMe-cHx) H H 1-1530 H H H Et 2—(CH₂)₆-(3,5-diMe-cHx) H H 1-1531 H H H Et 2 —(CH₂)₆-Ph H H 1-1532 H H HEt 2 —(CH₂)₆-Ph Me H 1-1533 H H H Et 2 —(CH₂)₆-Ph H Me 1-1534 H H H Et 2—(CH₂)₆-Ph F H 1-1535 H H H Et 2 —(CH₂)₆-Ph H F 1-1536 H H H Et 2—(CH₂)₆-(4-F-Ph) H H 1-1537 H H H Et 2 —(CH₂)₆-(4-Cl-Ph) H H 1-1538 H HH Et 2 —(CH₂)₆-(4-Br-Ph) H H 1-1539 H H H Et 2 —(CH₂)₆-(4-Me-Ph) H H1-1540 H H H Et 2 —(CH₂)₆-(4-Et-Ph) H H 1-1541 H H H Et 2—(CH₂)₆-(4-Pr-Ph) H H 1-1542 H H H Et 2 —(CH₂)₆-(4-iPr-Ph) H H 1-1543 HH H Et 2 —(CH₂)₆-(4-Bu-Ph) H H 1-1544 H H H Et 2 —(CH₂)₆-(4-CF₃-Ph) H H1-1545 H H H Et 2 —(CH₂)₆-(4-MeO-Ph) H H 1-1546 H H H Et 2—(CH₂)₆-(4-EtO-Ph) H H 1-1547 H H H Et 2 —(CH₂)₆-(4-PrO-Ph) H H 1-1548 HH H Et 2 —(CH₂)₆-(4-iPrO-Ph) H H 1-1549 H H H Et 2 —(CH₂)₆-(3-MeS-Ph) HH 1-1550 H H H Et 2 —(CH₂)₆-(4-MeS-Ph) H H 1-1551 H H H Et 2—(CH₂)₆-(2,4-diMe-Ph) H H 1-1552 H H H Et 2 —(CH₂)₆-(3,4-diMe-Ph) H H1-1553 H H H Et 2 —(CH₂)₆-(3,5-diMe-Ph) H H 1-1554 H H H Et 2—(CH₂)₇-cHx H H 1-1555 H H H Et 2 —(CH₂)₇-Ph H H 1-1556 H H H Et 2—C≡C—CH₂-cHx H H 1-1557 H H H Et 2 —C≡C—CH₂-Ph H H 1-1558 H H H Et 2—C≡C—(CH₂)₂-cHx H H 1-1559 H H H Et 2 —C≡C—(CH₂)₂-Ph H H 1-1560 H H H Et2 —C≡C—(CH₂)₃-cPn H H 1-1561 H H H Et 2 —C≡C—(CH₂)₃-cHx H H 1-1562 H H HEt 2 —C≡C—(CH₂)₃-cHx Me H 1-1563 H H H Et 2 —C≡C—(CH₂)₃-cHx H Me 1-1564H H H Et 2 —C≡C—(CH₂)₃-cHx F H 1-1565 H H H Et 2 —C≡C—(CH₂)₃-cHx H F1-1566 H H H Et 2 —C≡C—(CH₂)₃-(4-F-cHx) H H 1-1567 H H H Et 2—C≡C—(CH₂)₃-(4-Cl-cHx) H H 1-1568 H H H Et 2 —C≡C—(CH₂)₃-(4-Br-cHx) H H1-1569 H H H Et 2 —C≡C—(CH₂)₃-(4-Me-cHx) H H 1-1570 H H H Et 2—C≡C—(CH₂)₃-(4-Et-cHx) H H 1-1571 H H H Et 2 —C≡C—(CH₂)₃-(4-Pr-cHx) H H1-1572 H H H Et 2 —C≡C—(CH₂)₃-(4-iPr-cHx) H H 1-1573 H H H Et 2—C≡C—(CH₂)₃-(4-Bu-cHx) H H 1-1574 H H H Et 2 —C≡C—(CH₂)₃-(4-CF₃-cHx) H H1-1575 H H H Et 2 —C≡C—(CH₂)₃-(4-MeO-cHx) H H 1-1576 H H H Et 2—C≡C—(CH₂)₃-(4-EtO-cHx) H H 1-1577 H H H Et 2 —C≡C—(CH₂)₃-(4-PrO-cHx) HH 1-1578 H H H Et 2 —C≡C—(CH₂)₃-(4-iPrO-cHx) H H 1-1579 H H H Et 2—C≡C—(CH₂)₃-(3-MeS-cHx) H H 1-1580 H H H Et 2 —C≡C—(CH₂)₃-(4-MeS-cHx) HH 1-1581 H H H Et 2 —C≡C—(CH₂)₃-(2,4-diMe-cHx) H H 1-1582 H H H Et 2—C≡C—(CH₂)₃-(3,4-diMe-cHx) H H 1-1583 H H H Et 2—C≡C—(CH₂)₃-(3,5-diMe-cHx) H H 1-1584 H H H Et 2 —C≡C—(CH₂)₃-Ph H H1-1585 H H H Et 2 —C≡C—(CH₂)₃-Ph Me H 1-1586 H H H Et 2 —C≡C—(CH₂)₃-Ph HMe 1-1587 H H H Et 2 —C≡C—(CH₂)₃-Ph F H 1-1588 H H H Et 2 —C≡C—(CH₂)₃-PhH F 1-1589 H H H Et 2 —C≡C—(CH₂)₃-(4-F-Ph) H H 1-1590 H H H Et 2—C≡C—(CH₂)₃-(4-Cl-Ph) H H 1-1591 H H H Et 2 —C≡C—(CH₂)₃-(4-Br-Ph) H H1-1592 H H H Et 2 —C≡C—(CH₂)₃-(4-Me-Ph) H H 1-1593 H H H Et 2—C≡C—(CH₂)₃-(4-Et-Ph) H H 1-1594 H H H Et 2 —C≡C—(CH₂)₃-(4-Pr-Ph) H H1-1595 H H H Et 2 —C≡C—(CH₂)₃-(4-iPr-Ph) H H 1-1596 H H H Et 2—C≡C—(CH₂)₃-(4-Bu-Ph) H H 1-1597 H H H Et 2 —C≡C—(CH₂)₃-(4-CF₃-Ph) H H1-1598 H H H Et 2 —C≡C—(CH₂)₃-(4-MeO-Ph) H H 1-1599 H H H Et 2—C≡C—(CH₂)₃-(4-EtO-Ph) H H 1-1600 H H H Et 2 —C≡C—(CH₂)₃-(4-PrO-Ph) H H1-1601 H H H Et 2 —C≡C—(CH₂)₃-(4-iPrO-Ph) H H 1-1602 H H H Et 2—C≡C—(CH₂)₃-(3-MeS-Ph) H H 1-1603 H H H Et 2 —C≡C—(CH₂)₃-(4-MeS-Ph) H H1-1604 H H H Et 2 —C≡C—(CH₂)₃-(2,4-diMe-Ph) H H 1-1605 H H H Et 2—C≡C—(CH₂)₃-(3,4-diMe-Ph) H H 1-1606 H H H Et 2—C≡C—(CH₂)₃-(3,5-diMe-Ph) H H 1-1607 H H H Et 2 —C≡C—(CH₂)₄-cPn H H1-1608 H H H Et 2 —C≡C—(CH₂)₄-cHx H H 1-1609 H H H Et 2 —C≡C—(CH₂)₄-cHxMe H 1-1610 H H H Et 2 —C≡C—(CH₂)₄-cHx H Me 1-1611 H H H Et 2—C≡C—(CH₂)₄-cHx F H 1-1612 H H H Et 2 —C≡C—(CH₂)₄-cHx H F 1-1613 H H HEt 2 —C≡C—(CH₂)₄-(4-F-cHx) H H 1-1614 H H H Et 2 —C≡C—(CH₂)₄-(4-Cl-cHx)H H 1-1615 H H H Et 2 —C≡C—(CH₂)₄-(4-Br-cHx) H H 1-1616 H H H Et 2—C≡C—(CH₂)₄-(4-Me-cHx) H H 1-1617 H H H Et 2 —C≡C—(CH₂)₄-(4-Et-cHx) H H1-1618 H H H Et 2 —C≡C—(CH₂)₄-(4-Pr-cHx) H H 1-1619 H H H Et 2—C≡C—(CH₂)₄-(4-iPr-cHx) H H 1-1620 H H H Et 2 —C≡C—(CH₂)₄-(4-Bu-cHx) H H1-1621 H H H Et 2 —C≡C—(CH₂)₄-(4-CF₃-cHx) H H 1-1622 H H H Et 2—C≡C—(CH₂)₄-(4-MeO-cHx) H H 1-1623 H H H Et 2 —C≡C—(CH₂)₄-(4-EtO-cHx) HH 1-1624 H H H Et 2 —C≡C—(CH₂)₄-(4-PrO-cHx) H H 1-1625 H H H Et 2—C≡C—(CH₂)₄-(4-iPrO-cHx) H H 1-1626 H H H Et 2 —C≡C—(CH₂)₄-(4-MeS-cHx) HH 1-1627 H H H Et 2 —C≡C—(CH₂)₄-(2,4-diMe-cHx) H H 1-1628 H H H Et 2—C≡C—(CH₂)₄-(3,4-diMe-cHx) H H 1-1629 H H H Et 2—C≡C—(CH₂)₄-(3,5-diMe-cHx) H H 1-1630 H H H Et 2 —C≡C—(CH₂)₄-Ph H H1-1631 H H H Et 2 —C≡C—(CH₂)₄-Ph Me H 1-1632 H H H Et 2 —C≡C—(CH₂)₄-Ph HMe 1-1633 H H H Et 2 —C≡C—(CH₂)₄-Ph F H 1-1634 H H H Et 2 —C≡C—(CH₂)₄-PhH F 1-1635 H H H Et 2 —C≡C—(CH₂)₄-(4-F-Ph) H H 1-1636 H H H Et 2—C≡C—(CH₂)₄-(4-Cl-Ph) H H 1-1637 H H H Et 2 —C≡C—(CH₂)₄-(4-Br-Ph) H H1-1638 H H H Et 2 —C≡C—(CH₂)₄-(4-Me-Ph) H H 1-1639 H H H Et 2—C≡C—(CH₂)₄-(4-Et-Ph) H H 1-1640 H H H Et 2 —C≡C—(CH₂)₄-(4-Pr-Ph) H H1-1641 H H H Et 2 —C≡C—(CH₂)₄-(4-iPr-Ph) H H 1-1642 H H H Et 2—C≡C—(CH₂)₄-(4-Bu-Ph) H H 1-1643 H H H Et 2 —C≡C—(CH₂)₄-(4-CF₃-Ph) H H1-1644 H H H Et 2 —C≡C—(CH₂)₄-(4-MeO-Ph) H H 1-1645 H H H Et 2—C≡C—(CH₂)₄-(4-EtO-Ph) H H 1-1646 H H H Et 2 —C≡C—(CH₂)₄-(4-PrO-Ph) H H1-1647 H H H Et 2 —C≡C—(CH₂)₄-(4-iPrO-Ph) H H 1-1648 H H H Et 2—C≡C—(CH₂)₄-(3-MeS-Ph) H H 1-1649 H H H Et 2 —C≡C—(CH₂)₃-(4-MeS-Ph) H H1-1650 H H H Et 2 —C≡C—(CH₂)₄-(2,4-diMe-Ph) H H 1-1651 H H H Et 2—C≡C—(CH₂)₄-(3,4-diMe-Ph) H H 1-1652 H H H Et 2—C≡C—(CH₂)₄-(3,5-diMe-Ph) H H 1-1653 H H H Et 2 —C≡C—(CH₂)₅-cHx H H1-1654 H H H Et 2 —C≡C—(CH₂)₅-Ph H H 1-1655 H H H Et 2 —C≡C—(CH₂)₆-cHx HH 1-1656 H H H Et 2 —C≡C—(CH₂)₆-Ph H H 1-1657 H H H Et 2 —C≡C—CH₂O-cHx HH 1-1658 H H H Et 2 —C≡C—CH₂O-Ph H H 1-1659 H H H Et 2 —C≡C—(CH₂)₂O-cPnH H 1-1660 H H H Et 2 —C≡C—(CH₂)₂O-cHx H H 1-1661 H H H Et 2—C≡C—(CH₂)₂O-cHx Me H 1-1662 H H H Et 2 —C≡C—(CH₂)₂O-cHx H Me 1-1663 H HH Et 2 —C≡C—(CH₂)₂O-cHx F H 1-1664 H H H Et 2 —C≡C—(CH₂)₂O-cHx H F1-1665 H H H Et 2 —C≡C—(CH₂)₂O-(4-F-cHx) H H 1-1666 H H H Et 2—C≡C—(CH₂)₂O-(4-Cl-cHx) H H 1-1667 H H H Et 2 —C≡C—(CH₂)₂O-(4-Br-cHx) HH 1-1668 H H H Et 2 —C≡C—(CH₂)₂O-(4-Me-cHx) H H 1-1669 H H H Et 2—C≡C—(CH₂)₂O-(4-Et-cHx) H H 1-1670 H H H Et 2 —C≡C—(CH₂)₂O-(4-Pr-cHx) HH 1-1671 H H H Et 2 —C≡C—(CH₂)₂O-(4-iPr-cHx) H H 1-1672 H H H Et 2—C≡C—(CH₂)₂O-(4-Bu-cHx) H H 1-1673 H H H Et 2 —C≡C—(CH₂)₂O-(4-CF₃-cHx) HH 1-1674 H H H Et 2 —C≡C—(CH₂)₂O-(4-MeO-cHx) H H 1-1675 H H H Et 2—C≡C—(CH₂)₂O-(4-EtO-cHx) H H 1-1676 H H H Et 2 —C≡C—(CH₂)₂O-(4-PrO-cHx)H H 1-1677 H H H Et 2 —C≡C—(CH₂)₂O-(4-iPrO-cHx) H H 1-1678 H H H Et 2—C≡C—(CH₂)₂O-(3-MeS-cHx) H H 1-1679 H H H Et 2 —C≡C—(CH₂)₂O-(4-MeS-cHx)H H 1-1680 H H H Et 2 —C≡C—(CH₂)₂O-(2,4-diMe-cHx) H H 1-1681 H H H Et 2—C≡C—(CH₂)₂O-(3,4-diMe-cHx) H H 1-1682 H H H Et 2—C≡C—(CH₂)₂O-(3,5-diMe-cHx) H H 1-1683 H H H Et 2 —C≡C—(CH₂)₂O-Ph H H1-1684 H H H Et 2 —C≡C—(CH₂)₂O-Ph Me H 1-1685 H H H Et 2 —C≡C—(CH₂)₂O-PhH Me 1-1686 H H H Et 2 —C≡C—(CH₂)₂O-Ph F H 1-1687 H H H Et 2—C≡C—(CH₂)₂O-Ph H F 1-1688 H H H Et 2 —C≡C—(CH₂)₂O-(4-F-Ph) H H 1-1689 HH H Et 2 —C≡C—(CH₂)₂O-(4-Cl-Ph) H H 1-1690 H H H Et 2—C≡C—(CH₂)₂O-(4-Br-Ph) H H 1-1691 H H H Et 2 —C≡C—(CH₂)₂O-(4-Me-Ph) H H1-1692 H H H Et 2 —C≡C—(CH₂)₂O-(4-Et-Ph) H H 1-1693 H H H Et 2—C≡C—(CH₂)₂O-(4-Pr-Ph) H H 1-1694 H H H Et 2 —C≡C—(CH₂)₂O-(4-iPr-Ph) H H1-1695 H H H Et 2 —C≡C—(CH₂)₂O-(4-Bu-Ph) H H 1-1696 H H H Et 2—C≡C—(CH₂)₂O-(4-CF₃-Ph) H H 1-1697 H H H Et 2 —C≡C—(CH₂)₂O-(4-MeO-Ph) HH 1-1698 H H H Et 2 —C≡C—(CH₂)₂O-(4-EtO-Ph) H H 1-1699 H H H Et 2—C≡C—(CH₂)₂O-(4-PrO-Ph) H H 1-1700 H H H Et 2 —C≡C—(CH₂)₂O-(4-iPrO-Ph) HH 1-1701 H H H Et 2 —C≡C—(CH₂)₂O-(4-MeS-Ph) H H 1-1702 H H H Et 2—C≡C—(CH₂)₂O-(2,4-diMe-Ph) H H 1-1703 H H H Et 2—C≡C—(CH₂)₂O-(3,4-diMe-Ph) H H 1-1704 H H H Et 2—C≡C—(CH₂)₂O-(3,5-diMe-Ph) H H 1-1705 H H H Et 2 —CO—(CH₂)₃-cHx H H1-1706 H H H Et 2 —CO—(CH₂)₃-Ph H H 1-1707 H H H Et 2 —CO—(CH₂)₄-cHx H H1-1708 H H H Et 2 —CO—(CH₂)₄-Ph H H 1-1709 H H H Et 2 —CO—(CH₂)₅-cHx H H1-1710 H H H Et 2 —CO—(CH₂)₅-Ph H H 1-1711 H H H Et 2 —CH(OH)—(CH₂)₄-cHxH H 1-1712 H H H Et 2 —CH(OH)—(CH₂)₄-Ph H H 1-1713 H H H Et 2—CH(OH)—(CH₂)₅-cHx H H 1-1714 H H H Et 2 —CH(OH)—(CH₂)₅-Ph H H 1-1715 HH H Et 2 -4-(cHx-CH₂O)Ph H H 1-1716 H H H Et 2 -4-[cHx-(CH₂)₂O]Ph H H1-1717 H H H Et 2 -4-[cHx-(CH₂)₃O]Ph H H 1-1718 H H H Et 2 -(4-BzO-Ph) HH 1-1719 H H H Et 2 -(4-BzO-2-F-Ph) H H 1-1720 H H H Et 2-(4-BzO-3-F-Ph) H H 1-1721 H H H Et 2 -(4-BzO-2,3-diF-Ph) H H 1-1722 H HH Et 2 -(4-BzO-2-Cl-Ph) H H 1-1723 H H H Et 2 -(4-BzO-3-Cl-Ph) H H1-1724 H H H Et 2 -(4-BzO-2,3-diCl-Ph) H H 1-1725 H H H Et 2-(4-BzO-2-Me-Ph) H H 1-1726 H H H Et 2 -(4-BzO-3-Me-Ph) H H 1-1727 H H HEt 2 -(4-BzO-2,3-diMe-Ph) H H 1-1728 H H H Et 2 -4-[Ph-(CH₂)₂O]-Ph H H1-1729 H H H Et 2 -4-[Ph-(CH₂)₃O]-Ph H H 1-1730 H H H Pr 2 —(CH₂)₅-cHx HH 1-1731 H H H Pr 2 —(CH₂)₅-Ph H H 1-1732 H H H Pr 2 —(CH₂)₆-cHx H H1-1733 H H H Pr 2 —(CH₂)₆-Ph H H 1-1734 H H H Pr 2 —C≡C—CH₂-cHx H H1-1735 H H H Pr 2 —C≡C—(CH₂)₃-cHx H H 1-1736 H H H Pr 2 —C≡C—(CH₂)₃-Ph HH 1-1737 H H H Pr 2 —C≡C—(CH₂)₄-cHx H H 1-1738 H H H Pr 2 —C≡C—(CH₂)₄-PhH H 1-1739 H H H Pr 2 —C≡C—(CH₂)₂O-cHx H H 1-1740 H H H Pr 2—C≡C—(CH₂)₂O-Ph H H 1-1741 H H H Pr 2 -4-(cHx-CH₂O)Ph H H 1-1742 H H HPr 2 -(4-BzO-Ph) H H 1-1743 H H H Me 2 —(CH₂)₄-(3-F-Ph) H H 1-1744 H H HMe 2 —(CH₂)₄-(3,4-diF-Ph) H H 1-1745 H H H Me 2 —(CH₂)₄-(3,5-diF-Ph) H H1-1746 H H H Me 2 —(CH₂)₄-(3-Cl-Ph) H H 1-1747 H H H Me 2—(CH₂)₄-(4-Cl-Ph) H H 1-1748 H H H Me 2 —(CH₂)₄-(3,4-diCl-Ph) H H 1-1749H H H Me 2 —(CH₂)₄-(3,5-diCl-Ph) H H 1-1750 H H H Me 2 —(CH₂)₄-(3-Me-Ph)H H 1-1751 H H H Me 2 —(CH₂)₄-(3,4-diMe-Ph) H H 1-1752 H H H Me 2—(CH₂)₄-(3,5-diMe-Ph) H H 1-1753 H H H Me 2 —(CH₂)₄-(3-CF₃-Ph) H H1-1754 H H H Me 2 —(CH₂)₄-(3,4-diCF₃-Ph) H H 1-1755 H H H Me 2—(CH₂)₄-(3,5-diCF₃-Ph) H H 1-1756 H H H Me 2 —(CH₂)₄-(3-MeO-Ph) H H1-1757 H H H Me 2 —(CH₂)₄-(3,4-diMeo-Ph) H H 1-1758 H H H Me 2—(CH₂)₄-(3,5-diMeO-Ph) H H 1-1759 H H H Me 2 —(CH₂)₄-(3,4,5-triMeO-Ph) HH 1-1760 H H H Me 2 —(CH₂)₄-(3-Ac-Ph) H H 1-1761 H H H Me 2—(CH₂)₄-(4-Ac-Ph) H H 1-1762 H H H Me 2 —(CH₂)₅-(3,4-diF-Ph) H H 1-1763H H H Me 2 —(CH₂)₅-(3,5-diF-Ph) H H 1-1764 H H H Me 2 —(CH₂)₅-(3-Cl-Ph)H H 1-1765 H H H Me 2 —(CH₂)₅-(3,4-diCl-Ph) H H 1-1766 H H H Me 2—(CH₂)₅-(3,5-diCl-Ph) H H 1-1767 H H H Me 2 —(CH₂)₅-(3,4-diCF₃-Ph) H H1-1768 H H H Me 2 —(CH₂)₅-(3,5-diCF₃-Ph) H H 1-1769 H H H Me 2—(CH₂)₅-(3,4-diMeO-Ph) H H 1-1770 H H H Me 2 —(CH₂)₅-(3,5-diMeO-Ph) H H1-1771 H H H Me 2 —(CH₂)₅-(3,4,5-triMeO-Ph) H H 1-1772 H H H Me 2—(CH₂)₅-(3-Ac-Ph) H H 1-1773 H H H Me 2 —(CH₂)₅-(4-Ac-Ph) H H 1-1774 H HH Me 2 —(CH₂)₃—O-(3-F-Ph) H H 1-1775 H H H Me 2 —(CH₂)₃—O-(3,4-diF-Ph) HH 1-1776 H H H Me 2 —(CH₂)₃—O-(3,5-diF-Ph) H H 1-1777 H H H Me 2—(CH₂)₃—O-(3-Me-Ph) H H 1-1778 H H H Me 2 —(CH₂)₃—O-(3,4-diMe-Ph) H H1-1779 H H H Me 2 —(CH₂)₃—O-(3,5-diMe-Ph) H H 1-1780 H H H Me 2—(CH₂)₃—O-(3-CF₃-Ph) H H 1-1781 H H H Me 2 —(CH₂)₃—O-(3,4-diCF₃-Ph) H H1-1782 H H H Me 2 —(CH₂)₃—O-(3,5-diCF₃-Ph) H H 1-1783 H H H Me 2—(CH₂)₃—O-(3-MeO-Ph) H H 1-1784 H H H Me 2 —(CH₂)₃—O-(3,4-diMeO-Ph) H H1-1785 H H H Me 2 —(CH₂)₃—O-(3,5-diMeO-Ph) H H 1-1786 H H H Me 2—(CH₂)₃—O-(3,4,5-triMeO-Ph) H H 1-1787 H H H Me 2 —(CH₂)₃—O-(3-Ac-Ph) HH 1-1788 H H H Me 2 —(CH₂)₃—O-(4-Ac-Ph) H H 1-1789 H H H Me 2—(CH₂)₄—O-(3,4-diF-Ph) H H 1-1790 H H H Me 2 —(CH₂)₄—O-(3,5-diF-Ph) H H1-1791 H H H Me 2 —(CH₂)₄—O-(3,4-diMeO-Ph) H H 1-1792 H H H Me 2—(CH₂)₄—O-(3,5-diMeO-Ph) H H 1-1793 H H H Me 2—(CH₂)₄—O-(3,4,5-triMeO-Ph) H H 1-1794 H H H Me 2 —(CH₂)₄—O-(3-Ac-Ph) HH 1-1795 H H H Me 2 —(CH₂)₄—O-(4-Ac-Ph) H H 1-1796 H H H Me 2—C≡C—(CH₂)₂-(3-F-Ph) H H 1-1797 H H H Me 2 —C≡C—(CH₂)₂-(3,4-diF-Ph) H H1-1798 H H H Me 2 —C≡C—(CH₂)₂-(3,5-diF-Ph) H H 1-1799 H H H Me 2—C≡C—(CH₂)₂-(3-Cl-Ph) H H 1-1800 H H H Me 2 —C≡C—(CH₂)₂-(4-Cl-Ph) H H1-1801 H H H Me 2 —C≡C—(CH₂)₂-(3,4-diCl-Ph) H H 1-1802 H H H Me 2—C≡C—(CH₂)₂-(3,5-diCl-Ph) H H 1-1803 H H H Me 2 —C≡C—(CH₂)₂-(3-Me-Ph) HH 1-1804 H H H Me 2 —C≡C—(CH₂)₂-(3,4-diMe-Ph) H H 1-1805 H H H Me 2—C≡C—(CH₂)₂-(3,5-diMe-Ph) H H 1-1806 H H H Me 2 —C≡C—(CH₂)₂-(3-CF₃-Ph) HH 1-1807 H H H Me 2 —C≡C—(CH₂)₂-(3,4-diCF₃-Ph) H H 1-1808 H H H Me 2—C≡C—(CH₂)₂-(3,5-diCF₃-Ph) H H 1-1809 H H H Me 2 —C≡C—(CH₂)₂-(3-MeO-Ph)H H 1-1810 H H H Me 2 —C≡C—(CH₂)₂-(3,4-diMeO-Ph) H H 1-1811 H H H Me 2—C≡C—(CH₂)₂-(3,5-diMeO-Ph) H H 1-1812 H H H Me 2—C≡C—(CH₂)₂-(3,4,5-triMeO-Ph) H H 1-1813 H H H Me 2—C≡C—(CH₂)₂-(3-Ac-Ph) H H 1-1814 H H H Me 2 —C≡C—(CH₂)₂-(4-Ac-Ph) H H1-1815 H H H Me 2 —C≡C—(CH₂)₃-(3,4-diF-Ph) H H 1-1816 H H H Me 2—C≡C—(CH₂)₃-(3,5-diF-Ph) H H 1-1817 H H H Me 2 —C≡C—(CH₂)₃-(3-Cl-Ph) H H1-1818 H H H Me 2 —C≡C—(CH₂)₃-(3,4-diCl-Ph) H H 1-1819 H H H Me 2—C≡C—(CH₂)₃-(3,5-diCl-Ph) H H 1-1820 H H H Me 2—C≡C—(CH₂)₃-(3,4-diCF₃-Ph) H H 1-1821 H H H Me 2—C≡C—(CH₂)₃-(3,5-diCF₃-Ph) H H 1-1822 H H H Me 2—C≡C—(CH₂)₃-(3,4-diMeO-Ph) H H 1-1823 H H H Me 2—C≡C—(CH₂)₃-(3,5-diMeO-Ph) H H 1-1824 H H H Me 2—C≡C—(CH₂)₃-(3,4,5-triMeO-Ph) H H 1-1825 H H H Me 2—C≡C—(CH₂)₃-(3-Ac-Ph) H H 1-1826 H H H Me 2 —C≡C—(CH₂)₃-(4-Ac-Ph) H H1-1827 H H H Me 2 —C≡C—CH₂—O-(3-F-Ph) H H 1-1828 H H H Me 2—C≡C—CH₂—O-(3,4-diF-Ph) H H 1-1829 H H H Me 2 —C≡C—CH₂—O-(3,5-diF-Ph) HH 1-1830 H H H Me 2 —C≡C—CH₂—O-(3-Cl-Ph) H H 1-1831 H H H Me 2—C≡C—CH₂—O-(4-Cl-Ph) H H 1-1832 H H H Me 2 —C≡C—CH₂—O-(3,4-diCl-Ph) H H1-1833 H H H Me 2 —C≡C—CH₂—O-(3,5-diCl-Ph) H H 1-1834 H H H Me 2—C≡C—CH₂—O-(3-Me-Ph) H H 1-1835 H H H Me 2 —C≡C—CH₂—O-(2,4-diMe-Ph) H H1-1836 H H H Me 2 —C≡C—CH₂—O-(3,4-diMe-Ph) H H 1-1837 H H H Me 2—C≡C—CH₂—O-(3,5-diMe-Ph) H H 1-1838 H H H Me 2 —C≡C—CH₂—O-(3-CF₃-Ph) H H1-1839 H H H Me 2 —C≡C—CH₂—O-(3,4-diCF₃-Ph) H H 1-1840 H H H Me 2—C≡C—CH₂—O-(3,5-diCF₃-Ph) H H 1-1841 H H H Me 2 —C≡C—CH₂—O-(3-MeO-Ph) HH 1-1842 H H H Me 2 —C≡C—CH₂—O-(3,4-diMeO-Ph) H H 1-1843 H H H Me 2—C≡C—CH₂—O-(3,5-diMeO-Ph) H H 1-1844 H H H Me 2—C≡C—CH₂—O-(3,4,5-triMeO-Ph) H H 1-1845 H H H Me 2 —C≡C—CH₂—O-(3-Ac-Ph)H H 1-1846 H H H Me 2 —C≡C—CH₂—O-(4-Ac-Ph) H H 1-1847 H H H Me 2—C≡C—CH₂—O-(4-CO₂H-Ph) H H 1-1848 H H H Me 2 —C≡C—(CH₂)₂—O-(3,4-diF-Ph)H H 1-1849 H H H Me 2 —C≡C—(CH₂)₂—O-(3,5-diF-Ph) H H 1-1850 H H H Me 2—C≡C—(CH₂)₂—O-(3-Cl-Ph) H H 1-1851 H H H Me 2—C≡C—(CH₂)₂—O-(3,4-diCl-Ph) H H 1-1852 H H H Me 2—C≡C—(CH₂)₂—O-(3,5-diCl-Ph) H H 1-1853 H H H Me 2—C≡C—(CH₂)₂—O-(3,4-diCF₃-Ph) H H 1-1854 H H H Me 2—C≡C—(CH₂)₂—O-(3,5-diCF₃-Ph) H H 1-1855 H H H Me 2—C≡C—(CH₂)₂—O-(3,4-diMeO-Ph) H H 1-1856 H H H Me 2—C≡C—(CH₂)₂—O-(3,5-diMeO-Ph) H H 1-1857 H H H Me 2—C≡C—(CH₂)₂—O-(3,4,5-triMeO-Ph) H H 1-1858 H H H Me 2—C≡C—(CH₂)₂—O-(3-Ac-Ph) H H 1-1859 H H H Me 2 —C≡C—(CH₂)₂—O-(4-Ac-Ph) HH 1-1860 H H H Me 2 —CO—(CH₂)₃-(3-F-Ph) H H 1-1861 H H H Me 2—CO—(CH₂)₃-(4-F-Ph) H H 1-1862 H H H Me 2 —CO—(CH₂)₃-(3,4-diF-Ph) H H1-1863 H H H Me 2 —CO—(CH₂)₃-(3,5-diF-Ph) H H 1-1864 H H H Me 2—CO—(CH₂)₃-(3-Cl-Ph) H H 1-1865 H H H Me 2 —CO—(CH₂)₃-(4-Cl-Ph) H H1-1866 H H H Me 2 —CO—(CH₂)₃-(3,4-diCl-Ph) H H 1-1867 H H H Me 2—CO—(CH₂)₃-(3,5-diCl-Ph) H H 1-1868 H H H Me 2 —CO—(CH₂)₃-(3-Me-Ph) H H1-1869 H H H Me 2 —CO—(CH₂)₃-(4-Me-Ph) H H 1-1870 H H H Me 2—CO—(CH₂)₃-(3,4-diMe-Ph) H H 1-1871 H H H Me 2 —CO—(CH₂)₃-(3,5-diMe-Ph)H H 1-1872 H H H Me 2 —CO—(CH₂)₃-(3-Et-Ph) H H 1-1873 H H H Me 2—CO—(CH₂)₃-(4-Et-Ph) H H 1-1874 H H H Me 2 —CO—(CH₂)₃-(3-CF₃-Ph) H H1-1875 H H H Me 2 —CO—(CH₂)₃-(4-CF₃-Ph) H H 1-1876 H H H Me 2—CO—(CH₂)₃-(3,4-diCF₃-Ph) H H 1-1877 H H H Me 2—CO—(CH₂)₃-(3,5-diCF₃-Ph) H H 1-1878 H H H Me 2 —CO—(CH₂)₃-(3-MeO-Ph) HH 1-1879 H H H Me 2 —CO—(CH₂)₃-(4-MeO-Ph) H H 1-1880 H H H Me 2—CO—(CH₂)₃-(3,4-diMeO-Ph) H H 1-1881 H H H Me 2—CO—(CH₂)₃-(3,5-diMeO-Ph) H H 1-1882 H H H Me 2—CO—(CH₂)₃-(3,4,5-triMeO-Ph) H H 1-1883 H H H Me 2 —CO—(CH₂)₃-(4-MeS-Ph)H H 1-1884 H H H Me 2 —CO—(CH₂)₃-(3-Ac-Ph) H H 1-1885 H H H Me 2—CO—(CH₂)₃-(4-Ac-Ph) H H 1-1886 H H H Me 2 —CO—(CH₂)₄-(3-F-Ph) H H1-1887 H H H Me 2 —CO—(CH₂)₄-(3,4-diF-Ph) H H 1-1888 H H H Me 2—CO—(CH₂)₄-(3,5-diF-Ph) H H 1-1889 H H H Me 2 —CO—(CH₂)₄-(3-Cl-Ph) H H1-1890 H H H Me 2 —CO—(CH₂)₄-(4-Cl-Ph) H H 1-1891 H H H Me 2—CO—(CH₂)₄-(3,4-diCl-Ph) H H 1-1892 H H H Me 2 —CO—(CH₂)₄-(3,5-diCl-Ph)H H 1-1893 H H H Me 2 —CO—(CH₂)₄-(3-Me-Ph) H H 1-1894 H H H Me 2—CO—(CH₂)₄-(3,4-diMe-Ph) H H 1-1895 H H H Me 2 —CO—(CH₂)₄-(3,5-diMe-Ph)H H 1-1896 H H H Me 2 —CO—(CH₂)₄-(3-CF₃-Ph) H H 1-1897 H H H Me 2—CO—(CH₂)₄-(3,4-diCF₃-Ph) H H 1-1898 H H H Me 2—CO—(CH₂)₄-(3,5-diCF₃-Ph) H H 1-1899 H H H Me 2 —CO—(CH₂)₄-(3-MeO-Ph) HH 1-1900 H H H Me 2 —CO—(CH₂)₄-(3,4-diMeO-Ph) H H 1-1901 H H H Me 2—CO—(CH₂)₄-(3,5-diMeO-Ph) H H 1-1902 H H H Me 2—CO—(CH₂)₄-(3,4,5-triMeO-Ph) H H 1-1903 H H H Me 2 —CO—(CH₂)₄-(3-Ac-Ph)H H 1-1904 H H H Me 2 —CO—(CH₂)₄-(4-Ac-Ph) H H 1-1905 H H H Me 2—CH(OH)—(CH₂)₃-(3-F-Ph) H H 1-1906 H H H Me 2 —CH(OH)—(CH₂)₃-(4-F-Ph) HH 1-1907 H H H Me 2 —CH(OH)—(CH₂)₃-(3,4-diF-Ph) H H 1-1908 H H H Me 2—CH(OH)—(CH₂)₃-(3,5-diF-Ph) H H 1-1909 H H H Me 2—CH(OH)—(CH₂)₃-(3-Cl-Ph) H H 1-1910 H H H Me 2 —CH(OH)—(CH₂)₃-(4-Cl-Ph)H H 1-1911 H H H Me 2 —CH(OH)—(CH₂)₃-(3,4-diCl-Ph) H H 1-1912 H H H Me 2—CH(OH)—(CH₂)₃-(3,5-diCl-Ph) H H 1-1913 H H H Me 2—CH(OH)—(CH₂)₃-(3-Me-Ph) H H 1-1914 H H H Me 2 —CH(OH)—(CH₂)₃-(4-Me-Ph)H H 1-1915 H H H Me 2 —CH(OH)—(CH₂)₃-(3,4-diMe-Ph) H H 1-1916 H H H Me 2—CH(OH)—(CH₂)₃-(3,5-diMe-Ph) H H 1-1917 H H H Me 2—CH(OH)—(CH₂)₃-(3-Et-Ph) H H 1-1918 H H H Me 2 —CH(OH)—(CH₂)₃-(4-Et-Ph)H H 1-1919 H H H Me 2 —CH(OH)—(CH₂)₃-(3-CF₃-Ph) H H 1-1920 H H H Me 2—CH(OH)—(CH₂)₃-(4-CF₃-Ph) H H 1-1921 H H H Me 2—CH(OH)—(CH₂)₃-(3,4-diCF₃-Ph) H H 1-1922 H H H Me 2—CH(OH)—(CH₂)₃-(3,5-diCF₃-Ph) H H 1-1923 H H H Me 2—CH(OH)—(CH₂)₃-(3-MeO-Ph) H H 1-1924 H H H Me 2—CH(OH)—(CH₂)₃-(4-MeO-Ph) H H 1-1925 H H H Me 2—CH(OH)—(CH₂)₃-(3,4-diMeO-Ph) H H 1-1926 H H H Me 2—CH(OH)—(CH₂)₃-(3,5-diMeO-Ph) H H 1-1927 H H H Me 2—CH(OH)—(CH₂)₃-(3,4,5-triMeO-Ph) H H 1-1928 H H H Me 2—CH(OH)—(CH₂)₃-(4-MeS-Ph) H H 1-1929 H H H Me 2 —CH(OH)—(CH₂)₃-(3-Ac-Ph)H H 1-1930 H H H Me 2 —CH(OH)—(CH₂)₃-(4-Ac-Ph) H H 1-1931 H H H Me 2—CH(OH)—(CH₂)₄-(3-F-Ph) H H 1-1932 H H H Me 2—CH(OH)—(CH₂)₄-(3,4-diF-Ph) H H 1-1933 H H H Me 2—CH(OH)—(CH₂)₄-(3,5-diF-Ph) H H 1-1934 H H H Me 2—CH(OH)—(CH₂)₄-(3-Cl-Ph) H H 1-1935 H H H Me 2 —CH(OH)—(CH₂)₄-(4-Cl-Ph)H H 1-1936 H H H Me 2 —CH(OH)—(CH₂)₄-(3,4-diCl-Ph) H H 1-1937 H H H Me 2—CH(OH)—(CH₂)₄-(3,5-diCl-Ph) H H 1-1938 H H H Me 2—CH(OH)—(CH₂)₄-(3-Me-Ph) H H 1-1939 H H H Me 2—CH(OH)—(CH₂)₄-(3,4-diMe-Ph) H H 1-1940 H H H Me 2—CH(OH)—(CH₂)₄-(3,5-diMe-Ph) H H 1-1941 H H H Me 2—CH(OH)—(CH₂)₄-(3-CF₃-Ph) H H 1-1942 H H H Me 2—CH(OH)—(CH₂)₄-(3,4-diCF₃-Ph) H H 1-1943 H H H Me 2—CH(OH)—(CH₂)₄-(3,5-diCF₃-Ph) H H 1-1944 H H H Me 2—CH(OH)—(CH₂)₄-(3-MeO-Ph) H H 1-1945 H H H Me 2—CH(OH)—(CH₂)₄-(3,4-diMeO-Ph) H H 1-1946 H H H Me 2—CH(OH)—(CH₂)₄-(3,5-diMeo-Ph) H H 1-1947 H H H Me 2—CH(OH)—(CH₂)₄-(3,4,5-triMeO-Ph) H H 1-1948 H H H Me 2—CH(OH)—(CH₂)₄-(3-Ac-Ph) H H 1-1949 H H H Me 2 —CH(OH)—(CH₂)₄-(4-Ac-Ph)H H

TABLE 2

or

Compd. R¹ R² R³ R⁴ n —Y—Z—R⁵ R⁶ R⁷ 2-1 H H H Me 2 —(CH₂)₃-cHx H H 2-2 HH H Me 2 —(CH₂)₃-Ph H H 2-3 H H H Me 2 —(CH₂)₄-cHx H H 2-4 H H H Me 2—(CH₂)₄-Ph H H 2-5 H H H Me 2 —(CH₂)₅-cPn H H 2-6 H H H Me 2 —(CH₂)₅-cHxH H 2-7 H H H Me 2 —(CH₂)₅-cHx Me H 2-8 H H H Me 2 —(CH₂)₅-cHx H Me 2-9H H H Me 2 —(CH₂)₅-cHx F H 2-10 H H H Me 2 —(CH₂)₅-cHx H F 2-11 H H H Me2 —(CH₂)₅-(4-F-cHx) H H 2-12 H H H Me 2 —(CH₂)₅-(4-C1-CHx) H H 2-13 H HH Me 2 —(CH₂)₅-(4-Br-cHx) H H 2-14 H H H Me 2 —(CH₂)₅-(4-Me-cHx) H H2-15 H H H Me 2 —(CH₂)₅-(4-Et-cHx) H H 2-16 H H H Me 2—(CH₂)₅-(4-Pr-cHx) H H 2-17 H H H Me 2 —(CH₂)₅-(4-iPr-cHx) H H 2-18 H HH Me 2 —(CH₂)₅-(4-CF₃-cHx) H H 2-19 H H H Me 2 —(CH₂)₅-(4-MeO-cHx) H H2-20 H H H Me 2 —(CH₂)₅-(4-EtO-cHx) H H 2-21 H H H Me 2—(CH₂)₅-(4-PrO-cHx) H H 2-22 H H H Me 2 —(CH₂)₅-(4-iPrO-cHx) H H 2-23 HH H Me 2 —(CH₂)₅-(3-MeS-cHx) H H 2-24 H H H Me 2 —(CH₂)₅-(4-MeS-cHx) H H2-25 H H H Me 7 —(CH₂)₅-(2,4-diMe-cHx) H H 2-26 H H H Me 2—(CH₂)₅-(3,4-diMe-cHx) H H 2-27 H H H Me 2 —(CH₂)₅-(3,5-diMe-cHx) H H2-28 H H H Me 2 —(CH₂)₅-Ph H H 2-29 H H H Me 2 —(CH₂)₅-Ph Me H 2-30 H HH Me 2 —(CH₂)₅-Ph H Me 2-31 H H H Me 2 —(CH₂)₅-Ph F H 2-32 H H H Me 2—(CH₂)₅-Ph H F 2-33 H H H Me 2 —(CH₂)₅-(4-F-Ph) H H 2-34 H H H Me 2—(CH₂)₅-(4-Cl-Ph) H H 2-35 H H H Me 2 —(CH₂)₅- (4-Br-Ph) H H 2-36 H H HMe 2 —(CH₂)₅-(4-Me-Ph) H H 2-37 H H H Me 2 —(CH₂)₅-(4-Et-Ph) H H 2-38 HH H Me 2 —(CH₂)₅-(4-Pr-Ph) H H 2-39 H H H Me 2 —(CH₂)₅-(4-iPr-Ph) H H2-40 H H H Me 2 —(CH₂)₅-(4-Bu-Ph) H H 2-41 H H H Me 2 —(CH₂)₅-(4-CF₃-Ph)H H 2-42 H H H Me 2 —(CH₂)₅-(4-MeO-Ph) H H 2-43 H H H Me 2—(CH₂)₅-(4-EtO-Ph) H H 2-44 H H H Me 2 —(CH₂)₅-(4-PrO-Ph) H H 2-45 H H HMe 2 —(CH₂)₅-(4-iPrO-Ph) H H 2-46 H H H Me 2 —(CH₂)₅-(3-MeS-Ph) H H 2-47H H H Me 2 —(CH₂)₅-(4-MeS-Ph) H H 2-48 H H H Me 2 —(CH₂)₅-(2,4-diMe-Ph)H H 2-49 H H H Me 2 —(CH₂)₅-(3,4-diMe-Ph) H H 2-50 H H H Me 2—(CH₂)₅-(3,5-diMe-Ph) H H 2-51 H H H Me 2 —(CH₂)₆-cPn H H 2-52 H H H Me2 —(CH₂)₆-cHx H H 2-53 H H H Me 2 —(CH₂)₆-cHx Me H 2-54 H H H Me 2—(CH₂)₆-cHx H Me 2-55 H H H Me 2 —(CH₂)₆-cHx F H 2-56 H H H Me 2—(CH₂)₆-cHx H F 2-57 H H H Me 2 —(CH₂)₆-(4-F-cHx) H H 2-58 H H H Me 2—(CH₂)₆-(4-Cl-cHx) H H 2-59 H H H Me 2 —(CH₂)₆-(4-Br-cHx) H H 2-60 H H HMe 2 —(CH₂)₆-(4-Me-cHx) H H 2-61 H H H Me 2 —(CH₂)₆-(4-Et-cHx) H H 2-62H H H Me 2 —(CH₂)₆-(4-Pr-cHx) H H 2-63 H H H Me 2 —(CH₂)₆-(4-iPr-cHx) HH 2-64 H H H Me 2 —(CH₂)₆-(4-Bu-cHx) H H 2-65 H H H Me 2—(CH₂)₆-(4-CF₃-cHx) H H 2-66 H H H Me 2 —(CH₂)₆-(4-MeO-cHx) H H 2-67 H HH Me 2 —(CH₂)₆-(4-EtO-cHx) H H 2-68 H H H Me 2 —(CH₂)₆-(4-PrO-cHx) H H2-69 H H H Me 2 —(CH₂)₆-(4-iPrO-cHx) H H 2-70 H H H Me 2—(CH₂)₆-(3-MeS-cHx) H H 2-71 H H H Me 2 —(CH₂)₆-(4-MeS-cHx) H H 2-72 H HH Me 2 —(CH₂)₆-(2,4-diMe-cHx) H H 2-73 H H H Me 2 —(CH₂)₆-(3,4-diMe-cHx)H H 2-74 H H H Me 2 —(CH₂)₆-(3,5-diMe-cHx) H H 2-75 H H H Me 2—(CH₂)₆-Ph H H 2-76 H H H Me 2 —(CH₂)₆-Ph Me H 2-77 H H H Me 2—(CH₂)₆-Ph H Me 2-78 H H H Me 2 —(CH₂)₆-Ph F H 2-79 H H H Me 2—(CH₂)₆-Ph H F 2-80 H H H Me 2 —(CH₂)₆-(4-F-Ph) H H 2-81 H H H Me 2—(CH₂)₆-(4-Cl-Ph) H H 2-82 H H H Me 2 —(CH₂)₆-(4-Br-Ph) H H 2-83 H H HMe 2 —(CH₂)₆-(4-Me-Ph) H H 2-84 H H H Me 2 —(CH₂)₆-(4-Et-Ph) H H 2-85 HH H Me 2 —(CH₂)₆-(4-Pr-Ph) H H 2-86 H H H Me 2 —(CH₂)₆-(4-iPr-Ph) H H2-87 H H H Me 2 —(CH₂)₆-(4-Bu-Ph) H H 2-88 H H H Me 2 —(CH₂)₆-(4-CF₃-Ph)H H 2-89 H H H Me 2 —(CH₂)₆-(4-MeO-Ph) H H 2-90 H H H Me 2—(CH₂)₆-(4-EtO-Ph) H H 2-91 H H H Me 2 —(CH₂)₆-(4-PrO-Ph) H H 2-92 H H HMe 2 —(CH₂)₆-(4-iPrO-Ph) H H 2-93 H H H Me 2 —(CH₂)₆-(3-MeS-Ph) H H 2-94H H H Me 2 —(CH₂)₆-(4-MeS-Ph) H H 2-95 H H H Me 2 —(CH₂)₆-(2,4-diMe-Ph)H H 2-96 H H H Me 2 —(CH₂)₆-(3,4-diMe-Ph) H H 2-97 H H H Me 2—(CH₂)₆-(3,5-diMe-Ph) H H 2-98 H H H Me 2 —(CH₂)₇-cHx H H 2-99 H H H Me2 —(CH₂)₇-Ph H H 2-100 H H H Me 2 —(CH₂)₈-cHx H H 2-101 H H H Me 2—(CH₂)₈-Ph H H 2-102 H H H Me 2 —C≡C—CH₂-cHx H H 2-103 H H H Me 2—C≡C—CH₂-Ph H H 2-104 H H H Me 2 —C≡C—(CH₂)₂-cHx H H 2-105 H H H Me 2—C≡C—(CH₂)₂-Ph H H 2-106 H H H Me 2 —C≡C—(CH₂)₃-cPn H H 2-107 H H H Me 2—C≡C—(CH₂)₃-cHx H H 2-108 H H H Me 2 —C≡C—(CH₂)₃-cHx Me H 2-109 H H H Me2 —C≡C—(CH₂)₃-cHx H Me 2-110 H H H Me 2 —C≡C—(CH₂)₃-cHx F H 2-111 H H HMe 2 —C≡C—(CH₂)₃-cHx H F 2-112 H H H Me 2 —C≡C—(CH₂)₃-(4-F-cHx) H H2-113 H H H Me 2 —C≡C—(CH₂)₃-(4-Cl-cHx) H H 2-114 H H H Me 2—C≡C—(CH₂)₃-(4-Br-cHx) H H 2-115 H H H Me 2 —C≡C—(CH₂)₃-(4-Me-cHx) H H2-116 H H H Me 2 —C≡C—(CH₂)₃-(4-Et-cHx) H H 2-117 H H H Me 2—C≡C—(CH₂)₃-(4-Pr-cHx) H H 2-118 H H H Me 2 —C≡C—(CH₂)₃-(4-iPr-cHx) H H2-119 H H H Me 2 —C≡C—(CH₂)₃-(4-Bu-cHx) H H 2-120 H H H Me 2—C≡C—(CH₂)₃-(4-CF₃-cHx) H H 2-121 H H H Me 2 —C≡C—(CH₂)₃-(4-MeO-cHx) H H2-122 H H H Me 2 —C≡C—(CH₂)₃-(4-EtO-cHx) H H 2-123 H H H Me 2—C≡C—(CH₂)₃-(4-PrO-cHx) H H 2-124 H H H Me 2 —C≡C—(CH₂)₃-(4-iPrO-cHx) HH 2-125 H H H Me 2 —C≡C—(CH₂)₃-(3-MeS-cHx) H H 2-126 H H H Me 2—C≡C—(CH₂)₃-(4-MeS-cHx) H H 2-127 H H H Me 2 —C≡C—(CH₂)₃-(2,4-diMe-cHx)H H 2-128 H H H Me 2 —C≡C—(CH₂)₃-(3,4-diMe-cHx) H H 2-129 H H H Me 2—C≡C—(CH₂)₃-(3,5-diMe-cHx) H H 2-130 H H H Me 2 —C≡C—(CH₂)₃-Ph H H 2-131H H H Me 2 —C≡C—(CH₂)₃-Ph Me H 2-132 H H H Me 2 —C≡C—(CH₂)₃-Ph H Me2-133 H H H Me 2 —C≡C—(CH₂)₃-Ph F H 2-134 H H H Me 2 —C≡C—(CH₂)₃-Ph H F2-135 H H H Me 2 —C≡C—(CH₂)₃-(4-F-Ph) H H 2-136 H H H Me 2—C≡C—(CH₂)₃-(4-Cl-Ph) H H 2-137 H H H Me 2 —C≡C—(CH₂)₃-(4-Br-Ph) H H2-138 H H H Me 2 —C≡C—(CH₂)₃-(4-Me-Ph) H H 2-139 H H H Me 2—C≡C—(CH₂)₃-(4-Et-Ph) H H 2-140 H H H Me 2 —C≡C—(CH₂)₃-(4-Pr-Ph) H H2-141 H H H Me 2 —C≡C—(CH₂)₃-(4-iPr-Ph) H H 2-142 H H H Me 2—C≡C—(CH₂)₃-(4-Bu-Ph) H H 2-143 H H H Me 2 —C≡C—(CH₂)₃-(4-CF₃-Ph) H H2-144 H H H Me 2 —C≡C—(CH₂)₃-(4-MeO-Ph) H H 2-145 H H H Me 2—C≡C—(CH₂)₃-(4-EtO-Ph) H H 2-146 H H H Me 2 —C≡C—(CH₂)₃-(4-PrO-Ph) H H2-147 H H H Me 2 —C≡C—(CH₂)₃-(4-iPrO-Ph) H H 2-148 H H H Me 2—C≡C—(CH₂)₃-(3-MeS-Ph) H H 2-149 H H H Me 2 —C≡C—(CH₂)₃-(4-MeS-Ph) H H2-150 H H H Me 2 —C≡C—(CH₂)₃-(2,4-diMe-Ph) H H 2-151 H H H Me 2—C≡C—(CH₂)₃-(3,4-diMe-Ph) H H 2-152 H H H Me 2 —C≡C—(CH₂)₃-(3,5-diMe-Ph)H H 2-153 H H H Me 2 —C≡C—(CH₂)₄-cPn H H 2-154 H H H Me 2—C≡C—(CH₂)₄-cHx H H 2-155 H H H Me 2 —C≡C—(CH₂)₄-cHx Me H 2-156 H H H Me2 —C≡C—(CH₂)₄-cHx H Me 2-157 H H H Me 2 —C≡C—(CH₂)₄-cHx F H 2-158 H H HMe 2 —C≡C—(CH₂)₄-cHx H F 2-159 H H H Me 2 —C≡C—(CH₂)₄-(4-F-cHx) H H2-160 H H H Me 2 —C≡C—(CH₂)₄-(4-Cl-cHx) H H 2-161 H H H Me 2—C≡C—(CH₂)₄-(4-Br-cHx) H H 2-162 H H H Me 2 —C≡C—(CH₂)₄-(4-Me-cHx) H H2-163 H H H Me 2 —C≡C—(CH₂)₄-(4-Et-cHx) H H 2-164 H H H Me 2—C≡C—(CH₂)₄-(4-Pr-cHx) H H 2-165 H H H Me 2 —C≡C—(CH₂)₄-(4-iPr-cHx) H H2-166 H H H Me 2 —C≡C—(CH₂)₄-(4-Bu-cHx) H H 2-167 H H H Me 2—C≡C—(CH₂)₄-(4-CF₃-cHx) H H 2-168 H H H Me 2 —C≡C—(CH₂)₄-(4-MeO-cHx) H H2-169 H H H Me 2 —C≡C—(CH₂)₄-(4-EtO-cHx) H H 2-170 H H H Me 2—C≡C—(CH₂)₄-(4-PrO-cHx) H H 2-171 H H H Me 2 —C≡C—(CH₂)₄-(4-iPrO-cHx) HH 2-172 H H H Me 2 —C≡C—(CH₂)₄-(4-MeS-cHx) H H 2-173 H H H Me 2—C≡C—(CH₂)₄-(2,4-diMe-cHx) H H 2-174 H H H Me 2—C≡C—(CH₂)₄-(3,4-diMe-cHx) H H 2-175 H H H Me 2—C≡C—(CH₂)₄-(3,5-diMe-cHx) H H 2-176 H H H Me 2 —C≡C—(CH₂)₄-Ph H H 2-177H H H Me 2 —C≡C—(CH₂)₄-Ph Me H 2-178 H H H Me 2 —C≡C—(CH₂)₄-Ph H Me2-179 H H H Me 2 —C≡C—(CH₂)₄-Ph F H 2-180 H H H Me 2 —C≡C—(CH₂)₄-Ph H F2-181 H H H Me 2 —C≡C—(CH₂)₄-(4-F-Ph) H H 2-182 H H H Me 2—C≡C—(CH2.)₄-(4-Cl-Ph) H H 2-183 H H H Me 2 —C≡C—(CH₂)₄-(4-Br-Ph) H H2-184 H H H Me 2 —C≡C—(CH₂)₄-(4-Me-Ph) H H 2-185 H H H Me 2—C≡C—(CH₂)₄-(4-Et-Ph) H H 2-186 H H H Me 2 —C≡C—(CH₂)₄-(4-Pr-Ph) H H2-187 H H H Me 2 —C≡C—(CH₂)₄-(4-iPr-Ph) H H 2-188 H H H Me 2—C≡C—(CH₂)₄-(4-Bu-Ph) H H 2-189 H H H Me 2 —C≡C—(CH₂)₄-(4-CF₃-Ph) H H2-190 H H H Me 2 —C≡C—(CH₂)₄-(4-MeO-Ph) H H 2-191 H H H Me 2—C≡C—(CH₂)₄-(4-EtO-Ph) H H 2-192 H H H Me 2 —C≡C—(CH₂)₄-(4-PrO-Ph) H H2-193 H H H Me 2 —C≡C—(CH₂)₄-(4-iPrO-Ph) H H 2-194 H H H Me 2—C≡C—(CH₂)₄-(3-MeS-Ph) H H 2-195 H H H Me 2 —C≡C—(CH₂)₄-(4-MeS-Ph) H H2-196 H H H Me 2 —C≡C—(CH₂)₄-(2,4-diMe-Ph) H H 2-197 H H H Me 2—C≡C—(CH₂)₄-(3,4-diMe-Ph) H H 2-198 H H H Me 2 —C≡C—(CH₂)₄-(3,5-diMe-Ph)H H 2-199 H H H Me 2 —C≡C—(CH₂)₅-cHx H H 2-200 H H H Me 2 —C≡C—(CH₂)₅-PhH H 2-201 H H H Me 2 —C≡C—(CH₂)₆-cHx H H 2-202 H H H Me 2 —C≡C—(CH₂)₆-PhH H 2-203 H H H Me 2 —C≡C—CH₂O-cHx H H 2-204 H H H Me 2 —C≡C—CH₂O-Ph H H2-205 H H H Me 2 —C≡C—(CH₂)₂O-cPn H H 2-206 H H H Me 2 —C≡C—(CH₂)₂O-cHxH H 2-207 H H H Me 2 —C≡C—(CH₂)₂O-cHx Me H 2-208 H H H Me 2—C≡C—(CH₂)₂O-cHx H Me 2-209 H H H Me 2 —C≡C—(CH₂)₂O-cHx F H 2-210 H H HMe 2 —C≡C—(CH₂)₂O-cHx H F 2-211 H H H Me 2 —C≡C—(CH₂)₂O-(4-F-cHx) H H2-212 H H H Me 2 —C≡C—(CH₂)₂O-(4-Cl-cHx) H H 2-213 H H H Me 2—C≡C—(CH₂)2o-(4-Br-cHx) H H 2-214 H H H Me 2 —C≡C—(CH₂)₂O-(4-Me-cHx) H H2-215 H H H Me 2 —C≡C—(CH₂)₂O-(4-Et-cHx) H H 2-216 H H H Me 2—C≡C—(CH₂)₂O-(4-Pr-cHx) H H 2-217 H H H Me 2 —C≡C—(CH₂)₂O-(4-iPr-cHx) HH 2-218 H H H Me 2 —C≡C—(CH₂)₂O-(4-Bu-cHx) H H 2-219 H H H Me 2—C≡C—(CH₂)₂O-(4-CF₃-cHx) H H 2-220 H H H Me 2 —C≡C—(CH₂)₂O-(4-MeO-cHx) HH 2-221 H H H Me 2 —C≡C—(CH₂)₂O-(4-EtO-cHx) H H 2-222 H H H Me 2—C≡C—(CH₂)₂O-(4-PrO-cHx) H H 2-223 H H H Me 2 —C≡C—(CH₂)₂O-(4-iPrO-cHx)H H 2-224 H H H Me 2 —C≡C—(CH₂)₂O-(3-MeS-cHx) H H 2-225 H H H Me 2—C≡C—(CH₂)₂O-(4-MeS-cHx) H H 2-226 H H H Me 2 —C≡C—(CH₂)₂O-(2,4-diMe- HH cHx) 2-227 H H H Me 2 —C≡C—(CH₂)₂O-(3,4-diMe- H H cHx) 2-228 H H H Me2 —C≡C—(CH₂)₂O-(3,5-diMe- H H cHx) 2-229 H H H Me 2 —C≡C—(CH₂)₂O-Ph H H2-230 H H H Me 2 —C≡C—(CH₂)₂O-Ph Me H 2-231 H H H Me 2 —C≡C—(CH₂)₂O-Ph HMe 2-232 H H H Me 2 —C≡C—(CH₂)₂O-Ph F H 2-233 H H H Me 2 —C≡C—(CH₂)₂O-PhH F 2-234 H H H Me 2 —≡C—(CH₂)₂O-(4-F-Ph) H H 2-235 H H H Me 2—C≡C—(CH₂)₂O-(4-Cl-Ph) H H 2-236 H H H Me 2 —C≡C—(CH₂)₂O-(4-Br-Ph) H H2-237 H H H Me 2 —C≡C—(CH₂)₂O-(4-Me-Ph) H H 2-238 H H H Me 2—C≡C—(CH₂)₂O-(4-Et-Ph) H H 2-239 H H H Me 2 —C≡C—(CH₂)₂O-(4-Pr-Ph) H H2-240 H H H Me 2 —C≡C—(CH₂)₂O-(4-iPr-Ph) H H 2-241 H H H Me 2—C≡C—(CH₂)₂O-(4-Bu-Ph) H H 2-242 H H H Me 2 —C≡C—(CH₂)₂O-(4-CF₃-Ph) H H2-243 H H H Me 2 —C≡C—(CH₂)₂O-(4-MeO-Ph) H H 2-244 H H H Me 2—C≡C—(CH₂)₂O-(4-EtO-Ph) H H 2-245 H H H Me 2 —C≡C—(CH₂)₂O-(4-PrO-Ph) H H2-246 H H H Me 2 —C≡C—(CH₂)₂O-(4-iPrO-Ph) H H 2-247 H H H Me 2—C≡C—(CH₂)₂O-(4-MeS-Ph) H H 2-248 H H H Me 2 —C≡C—(CH₂)₂O-(2,4-diMe-Ph)H H 2-249 H H H Me 2 —C≡C—(CH₂)₂O-(3,4-diMe-Ph) H H 2-250 H H H Me 2—C≡C—(CH₂)₂O-(3,5-diMe-Ph) H H 2-251 H H H Me 2 —CO—(CH₂)₄-cHx H H 2-252H H H Me 2 —CO—(CH₂)₄-Ph H H 2-253 H H H Me 2 —CO—(CH₂)₅-cHx H H 2-254 HH H Me 2 —CO—(CH₂)₅-Ph H H 2-255 H H H Me 2 —CH(OH)—(CH₂)₄-cHx H H 2-256H H H Me 2 —CH(OH)—(CH₂)₄-Ph H H 2-257 H H H Me 2 —CH(OH)—(CH₂)₅-cHx H H2-258 H H H Me 2 —CH(OH)—(CH₂)₅-Ph H H 2-259 H H H Me 2 -4-(cHx-CH₂O)PhH H 2-260 H H H Me 2 -4-[cHx—(CH₂)₂O]Ph H H 2-261 H H H Me 2-4-[cHx—(CH₂)₃O]Ph H H 2-262 H H H Me 2 -(4-BzO-Ph) H H 2-263 H H H Me 2-(4-BzO-2-F-Ph) H H 2-264 H H H Me 2 -(4-BzO-3-F-Ph) H H 2-265 H H H Me2 -(4-BzO-2,3-diF-Ph) H H 2-266 H H H Me 2 -(4-BzO-2-Cl-Ph) H H 2-267 HH H Me 2 -(4-BzO-3-Cl-Ph) H H 2-268 H H H Me 2 -(4-BzO-2,3-diCl-Ph) H H2-269 H H H Me 2 -(4-BzO-2-Me-Ph) H H 2-270 H H H Me 2 -(4-BzO-3-Me-Ph)H H 2-271 H H H Me 2 -(4-BzO-2,3-diMe-Ph) H H 2-272 H H H Me 2-4-[Ph-(CH₂)₂O]-Ph H H 2-273 H H H Me 2 -3-[cHx-(CH₂)₂O]-Ph H H 2-274 HH H Et 2 —(CH₂)₅-cHx H H 2-275 H H H Et 2 —(CH₂)₆-cHx H H 2-276 H H H Et2 —C≡C—(CH₂)₃-cHx H H 2-277 H H H Et 2 —C≡C—(CH₂)₄-cHx H H 2-278 H H HEt 2 -4-(cHx-CH₂O)Ph H H 2-279 H H H Et 2 -(4-BzO-Ph) H H 2-280 H H H Et2 —C≡C—(CH₂)₂O-cHx H H 2-281 H H H Et 2 —C≡C—(CH₂)₂O-Ph H H 2-282 H H HPr 2 —(CH₂)₅-cHx H H 2-283 H H H Pr 2 —(CH₂)₆-cHx H H 2-284 H H H Pr 2—C≡C—(CH₂)₃-cHx H H 2-285 H H H Pr 2 —C≡C—(CH₂)₄-cHx H H 2-286 H H H Pr2 -4-(cHx-CH₂O)Ph H H 2-287 H H H Pr 2 -(4-BzO-Ph) H H 2-288 H H H Pr 2—C≡C—(CH₂)₂O-cHx H H 2-289 H H H Pr 2 —C≡C—(CH₂)₂O-Ph H H

TABLE 3

Compd. R¹ R² R³ R⁴ n —Y—Z—R⁵ R⁶ R⁷ 3-1 H H H Me 2 —(CH₂)₄-cHx H H 3-2 HH H Me 2 —(CH₂)₄-Ph H H 3-3 H H H Me 2 —(CH₂)₅-cHx H H 3-4 H H H Me 2—(CH₂)₅-Ph H H 3-5 H H H Me 2 —C≡C—(CH₂)₂-cHx H H 3-6 H H H Me 2—C≡C—(CH₂)₂-Ph H H 3-7 H H H Me 2 —C≡C—(CH₂)₃-cHx H H 3-8 H H H Me 2—C≡C—(CH₂)₃-Ph H H 3-9 H H H Me 2 —CO—(CH₂)₃-cHx H H 3-10 H H H Me 2—CO—(CH₂)₃-Ph H H 3-11 H H H Me 2 —CO—(CH₂)₄-cHx H H 3-12 H H H Me 2—CO—(CH₂)₄-Ph H H

TABLE 4

Compd. R¹ R² R³ R⁴ n —Y—Z—R⁵ R⁶ R⁷ 4-1 H H H Me 2 —(CH₂)₄-cHx H H 4-2 HH H Me 2 —(CH₂)₄-Ph H H 4-3 H H H Me 2 —(CH₂)₅-cHx H H 4-4 H H H Me 2—(CH₂)₅-Ph H H 4-5 H H H Me 2 —C≡C—(CH₂)₂-cHx H H 4-6 H H H Me 2—C≡C—(CH₂)₂-Ph H H 4-7 H H H Me 2 —C≡C—(CH₂)₃-cHx H H 4-8 H H H Me 2—C≡C—(CH₂)₃-Ph H H 4-9 H H H Me 2 —CO—(CH₂)₃-cHx H H 4-10 H H H Me 2—CO—(CH₂)₃-Ph H H 4-11 H H H Me 2 —CO—(CH₂)₄-cHx H H 4-12 H H H Me 2—CO—(CH₂)₄-Ph H H

TABLE 5

or

Compd. R¹ R² R⁴ n —Y—Z—R⁵ R⁶ R⁷ R¹⁰ R¹¹ 5-1 H H Me 1 —(CH₂)₅-cHx H H H H5-2 H H Me 1 —(CH₂)₆-cHx H H H H 5-3 H H Me 1 —CH═CH—(CH₂)₃-cHx H H H H5-4 H H Me 1 —CH═CH—(CH₂)₄-cHx H H H H 5-5 H H Me 1 —C≡C—(CH₂)₃-cHx H HH H 5-6 H H Me 1 —C≡C—(CH₂)₄-cHx H H H H 5-7 H H Me 1 —CO—(CH₂)₄-cHx H HH H 5-8 H H Me 1 —CO—(CH₂)₅-cHx H H H H 5-9 H H Me 1 —CH(OH)—(CH₂)₄-cHxH H H H 5-10 H H Me 1 —CH(OH)—(CH₂)₅-cHx H H H H 5-11 H H Me 1-4-(cHx-CH₂O)Ph H H H H 5-12 H H Me 1 -(4-BzO-Ph) H H H H 5-13 H H Me 1—C≡C—CH₂O-cPn H H H H 5-14 H H Me 1 —C≡C—(CH₂)₂O-cPn H H H H 5-15 H H Me1 —C≡C—CH₂O-cHx H H H H 5-16 H H Me 1 —C≡C—(CH₂)₂O-cHx H H H H 5-17 H HMe 1 —C≡C—CH₂O-Ph H H H H 5-18 H H Me 1 —C≡C—(CH₂)₂O-Ph H H H H 5-19 H HMe 2 —(CH₂)₂-cHx H H H H 5-20 H Me Me 2 —(CH₂)₂-cHx H H H H 5-21 CO₂Me HMe 2 —(CH₂)₂-cHx H H H H 5-22 CO₂Et H Me 2 —(CH₂)₂-cHx H H H H 5-23 H HMe 2 —(CH₂)₂-(4-F-cHx) H H H H 5-24 H H Me 2 —(CH₂)₂-(4-Me-cHx) H H H H5-25 H H Me 2 —(CH₂)₂-(4-Et-cHx) H H H H 5-26 H H Me 2—(CH₂)₂-(4-CF₃-cHx) H H H H 5-27 H H Me 2 —(CH₂)₂-(4-MeO-cHx) H H H H5-28 H H Me 2 —(CH₂)₂-(4-EtO-cHx) H H H H 5-29 H H Me 2—(CH₂)₂-(4-MeS-cHx) H H H H 5-30 H H Me 2 —(CH₂)₂-(4-cHx-cHx) H H H H5-31 H H Me 2 —(CH₂)₂-(4-Ph-cHx) H H H H 5-32 H H Me 2 —(CH₂)₂-Ph H H HH 5-33 H Me Me 2 —(CH₂)₂-Ph H H H H 5-34 CO₂Me H Me 2 —(CH₂)₂-Ph H H H H5-35 CO₂Et H Me 2 —(CH₂)₂-Ph H H H H 5-36 H H Me 2 —(CH₂)₂-(4-F-Ph) H HH H 5-37 H H Me 2 —(CH₂)₂-(4-Me-Ph) H H H H 5-38 H H Me 2—(CH₂)₂-(4-Et-Ph) H H H H 5-39 H H Me 2 —(CH₂)₂-(4-CF₃-Ph) H H H H 5-40H H Me 2 —(CH₂)₂-(4-MeO-Ph) H H H H 5-41 H H Me 2 —(CH₂)₂-(4-EtO-Ph) H HH H 5-42 H H Me 2 —(CH₂)₂-(4-MeS-Ph) H H H H 5-43 H H Me 2—(CH₂)₂-(4-cHx-Ph) H H H H 5-44 H H Me 2 —(CH₂)₂-(4-Ph-Ph) H H H H 5-45H H Me 2 —(CH₂)₃-cHx H H H H 5-46 H Me Me 2 —(CH₂)₃-cHx H H H H 5-47CO₂Me H Me 2 —(CH₂)₃-cHx H H H H 5-48 CO₂Et H Me 2 —(CH₂)₃-cHx H H H H5-49 H H Me 2 —(CH₂)₃-(4-F-cHx) H H H H 5-50 H H Me 2 —(CH₂)₃-(4-Me-cHx)H H H H 5-51 H H Me 2 —(CH₂)₃-(4-Et-cHx) H H H H 5-52 H H Me 2—(CH₂)₃-(4-CF₃-cHx) H H H H 5-53 H H Me 2 —(CH₂)₃-(4-MeO-cHx) H H H H5-54 H H Me 2 —(CH₂)₃-(4-EtO-cHx) H H H H 5-55 H H Me 2—(CH₂)₃-(4-MeS-cHx) H H H H 5-56 H H Me 2 —(CH₂)₃-(4-cHx-cHx) H H H H5-57 H H Me 2 —(CH₂)₃-(4-Ph-cHx) H H H H 5-58 H H Me 2 —(CH₂)₃-Ph H H HH 5-59 H Me Me 2 —(CH₂)₃-Ph H H H H 5-60 CO₂Me H Me 2 —(CH₂)₃-Ph H H H H5-61 CO₂Et H Me 2 —(CH₂)₃-Ph H H H H 5-62 H H Me 2 —(CH₂)₃-(4-F-Ph) H HH H 5-63 H H Me 2 —(CH₂)₃-(4-Me-Ph) H H H H 5-64 H H Me 2—(CH₂)₃-(4-Et-Ph) H H H H 5-65 H H Me 2 —(CH₂)₃-(4-CF₃-Ph) H H H H 5-66H H Me 2 —(CH₂)₃-(4-MeO-Ph) H H H H 5-67 H H Me 2 —(CH₂)₃-(4-EtO-Ph) H HH H 5-68 H H Me 2 —(CH₂)₃-(4-MeS-Ph) H H H H 5-69 H H Me 2—(CH₂)₃-(4-cHx-Ph) H H H H 5-70 H H Me 2 —(CH₂)₃-(4-Ph-Ph) H H H H 5-71H H Me 2 —(CH₂)₄-cHx H H H H 5-72 H Me Me 2 —(CH₂)₄-cHx H H H H 5-73CO₂Me H Me 2 —(CH₂)₄-cHx H H H H 5-74 CO₂Et H Me 2 —(CH₂)₄-cHx H H H H5-75 H H Me 2 —(CH₂)₄-(4-F-cHx) H H H H 5-76 H H Me 2 —(CH₂)₄-(4-Me-cHx)H H H H 5-77 H H Me 2 —(CH₂)₄-(4-Et-cHx) H H H H 5-78 H H Me 2—(CH₂)₄-(4-CF₃-cHx) H H H H 5-79 H H Me 2 —(CH₂)₄-(4-MeO-cHx) H H H H5-80 H H Me 2 —(CH₂)₄-(4-EtO-cHx) H H H H 5-81 H H Me 2—(CH₂)₄-(4-MeS-cHx) H H H H 5-82 H H Me 2 —(CH₂)₄-(4-cHx-cHx) H H H H5-83 H H Me 2 —(CH₂)₄-(4-Ph-cHx) H H H H 5-84 H H Me 2 —(CH₂)₄-Ph H H HH 5-85 H Me Me 2 —(CH₂)₄-Ph H H H H 5-86 CO₂Me H Me 2 —(CH₂)₄-Ph H H H H5-87 CO₂Et H Me 2 —(CH₂)₄-Ph H H H H 5-88 H H Me 2 —(CH₂)₄-(4-F-Ph) H HH H 5-89 H H Me 2 —(CH₂)₄-(4-Me-Ph) H H H H 5-90 H H Me 2—(CH₂)₄-(4-Et-Ph) H H H H 5-91 H H Me 2 —(CH₂)₄-(4-CF₃-Ph) H H H H 5-92H H Me 2 —(CH₂)₄-(4-MeO-Ph) H H H H 5-93 H H Me 2 —(CH₂)₄-(4-EtO-Ph) H HH H 5-94 H H Me 2 —(CH₂)₄-(4-MeS-Ph) H H H H 5-95 H H Me 2—(CH₂)₄-(4-cHx-Ph) H H H H 5-96 H H Me 2 —(CH₂)₄-(4-Ph-Ph) H H H H 5-97H H Me 2 —(CH₂)₅-cPn H H H H 5-98 H H Me 2 —(CH₂)₅-cHx H H H H 5-99 H HMe 2 —(CH₂)₅-cHx Me H H H 5-100 H H Me 2 —(CH₂)₅-cHx H Me H H 5-101 H HMe 2 —(CH₂)₅-cHx F H H H 5-102 H H Me 2 —(CH₂)₅-cHx H F H H 5-103 H MeMe 2 —(CH₂)₅-cHx H H H H 5-104 CO₂Me H Me 2 —(CH₂)₅-cHx H H H H 5-105CO₂Et H Me 2 —(CH₂)₅-cHx H H H H 5-106 H H Me 2 —(CH₂)₅-(3-F-cHx) H H HH 5-107 H H Me 2 —(CH₂)₅-(4-F-cHx) H H H H 5-108 H H Me 2—(CH₂)₅-(4-Cl-cHx) H H H H 5-109 H H Me 2 —(CH₂)₅-(4-Br-cHx) H H H H5-110 H H Me 2 —(CH₂)₅-(3-Me-cHx) H H H H 5-111 H H Me 2—(CH₂)₅-(4-Me-cHx) H H H H 5-112 H H Me 2 —(CH₂)₅-(3-Et-cHx) H H H H5-113 H H Me 2 —(CH₂)₅-(4-Et-cHx) H H H H 5-114 H H Me 2—(CH₂)₅-(3-Pr-cHx) H H H H 5-115 H H Me 2 —(CH₂)₅-(4-Pr-cHx) H H H H5-116 H H Me 2 —(CH₂)₅-(4-iPr-cHx) H H H H 5-117 H H Me 2—(CH₂)₅-(3-Bu-cHx) H H H H 5-118 H H Me 2 —(CH₂)₅-(4-Bu-cHx) H H H H5-119 H H Me 2 —(CH₂)₅-(3-CF₃-cHx) H H H H 5-120 H H Me 2—(CH₂)₅-(4-CF₃-cHx) H H H H 5-121 H H Me 2 —(CH₂)₅-(3-MeO-cHx) H H H H5-122 H H Me 2 —(CH₂)₅-(4-MeO-cHx) H H H H 5-123 H H Me 2—(CH₂)₅-(3-EtO-cHx) H H H H 5-124 H H Me 2 —(CH₂)₅-(4-EtO-cHx) H H H H5-125 H H Me 2 —(CH₂)₅-(3-PrO-cHx) H H H H 5-126 H H Me 2—(CH₂)₅-(4-PrO-cHx) H H H H 5-127 H H Me 2 —(CH₂)₅-(3-iPrO-cHx) H H H H5-128 H H Me 2 —(CH₂)₅-(4-iPrO-cHx) H H H H 5-129 H H Me 2—(CH₂)₅-[3-(2-Et-PrO)-cHx] H H H H 5-130 H H Me 2—(CH₂)₅-[4-(2-Et-PrO)-cHx] H H H H 5-131 H H Me 2 —(CH₂)₅-(3-iBuO-cHx) HH H H 5-132 H H Me 2 —(CH₂)₅-(4-iBuO-cHx) H H H H 5-133 H H Me 2—(CH₂)₅-(3-MeS-cHx) H H H H 5-134 H H Me 2 —(CH₂)₅-(4-MeS-cHx) H H H H5-135 H H Me 2 —(CH₂)₅-(3-EtS-cHx) H H H H 5-136 H H Me 2—(CH₂)₅-(4-EtS-cHx) H H H H 5-137 H H Me 2 —(CH₂)₅-(3-PrS-cHx) H H H H5-138 H H Me 2 —(CH₂)₅-(4-PrS-cHx) H H H H 5-139 H H Me 2—(CH₂)₅-(3-iPrS-cHx) H H H H 5-140 H H Me 2 —(CH₂)₅-(4-iPrS-cHx) H H H H5-141 H H Me 2 —(CH₂)₅-[3-(2-Et-PrS)-cHx] H H H H 5-142 H H Me 2—(CH₂)₅-[4-(2-Et-PrS)-cHx] H H H H 5-143 H H Me 2 —(CH₂)₅-(3-iBuS-cHx) HH H H 5-144 H H Me 2 —(CH₂)₅-(4-iBuS-cHx) H H H H 5-145 H H Me 2—(CH₂)₅-(3-cHx-cHx) H H H H 5-146 H H Me 2 —(CH₂)₅-(4-cHx-cHx) H H H H5-147 H H Me 2 —(CH₂)₅-(3-Ph-cHx) H H H H 5-148 H H Me 2—(CH₂)₅-(4-Ph-cHx) H H H H 5-149 H H Me 2 —(CH₂)₅-(2,4-diMe-cHx) H H H H5-150 H H Me 2 —(CH₂)₅-(3,4-diMe-cHx) H H H H 5-151 H H Me 2—(CH₂)₅-(3,5-diMe-cHx) H H H H 5-152 H H Me 2 —(CH₂)₅-Ph H H H H 5-153 HH Me 2 —(CH₂)₅-Ph Me H H H 5-154 H H Me 2 —(CH₂)₅-Ph H Me H H 5-155 H HMe 2 —(CH₂)₅-Ph F H H H 5-156 H H Me 2 —(CH₂)₅-Ph H F H H 5-157 H Me Me2 —(CH₂)₅-Ph H H H H 5-158 CO₂Me H Me 2 —(CH₂)₅-Ph H H H H 5-159 CO₂Et HMe 2 —(CH₂)₅-Ph H H H H 5-160 H H Me 2 —(CH₂)₅-(3-F-Ph) H H H H 5-161 HH Me 2 —(CH₂)₅-(4-F-Ph) H H H H 5-162 H H Me 2 —(CH₂)₅-(4-Cl-Ph) H H H H5-163 H H Me 2 —(CH₂)₅-(4-Br-Ph) H H H H 5-164 H H Me 2—(CH₂)₅-(3-Me-Ph) H H H H 5-165 H H Me 2 —(CH₂)₅-(4-Me-Ph) H H H H 5-166H H Me 2 —(CH₂)₅-(3-Et-Ph) H H H H 5-167 H H Me 2 —(CH₂)₅-(4-Et-Ph) H HH H 5-168 H H Me 2 —(CH₂)₅-(3-Pr-Ph) H H H H 5-169 H H Me 2—(CH₂)₅-(4-Pr-Ph) H H H H 5-170 H H Me 2 —(CH₂)₅-(3-iPr-Ph) H H H H5-171 H H Me 2 —(CH₂)₅-(4-iPr-Ph) H H H H 5-172 H H Me 2—(CH₂)₅-(3-Bu-Ph) H H H H 5-173 H H Me 2 —(CH₂)₅-(4-Bu-Ph) H H H H 5-174H H Me 2 —(CH₂)₅-(3-CF₃-Ph) H H H H 5-175 H H Me 2 —(CH₂)₅-(4-CF₃-Ph) HH H H 5-176 H H Me 2 —(CH₂)₅-(3-MeO-Ph) H H H H 5-177 H H Me 2—(CH₂)₅-(4-MeO-Ph) H H H H 5-178 H H Me 2 —(CH₂)₅-(3-EtO-Ph) H H H H5-179 H H Me 2 —(CH₂)₅-(4-EtO-Ph) H H H H 5-180 H H Me 2—(CH₂)₅-(3-PrO-Ph) H H H H 5-181 H H Me 2 —(CH₂)₅-(4-PrO-Ph) H H H H5-182 H H Me 2 —(CH₂)₅-(3-iPrO-Ph) H H H H 5-183 H H Me 2—(CH₂)₅-(4-iPrO-Ph) H H H H 5-184 H H Me 2 —(CH₂)₅-[3-(2-Et-PrO)-Ph] H HH H 5-185 H H Me 2 —(CH₂)₅-[4-(2-Et-PrO)-Ph] H H H H 5-186 H H Me 2—(CH₂)₅-(3-iBuO-Ph) H H H H 5-187 H H Me 2 —(CH₂)₅-(4-iBuO-Ph) H H H H5-188 H H Me 2 —(CH₂)₅-(3-MeS-Ph) H H H H 5-189 H H Me 2—(CH₂)₅-(4-MeS-Ph) H H H H 5-190 H H Me 2 —(CH₂)₅-(3-EtS-Ph) H H H H5-191 H H Me 2 —(CH₂)₅-(4-EtS-Ph) H H H H 5-192 H H Me 2—(CH₂)₅-(3-PrS-Ph) H H H H 5-193 H H Me 2 —(CH₂)₅-(4-PrS-Ph) H H H H5-194 H H Me 2 —(CH₂)₅-(3-iPrS-Ph) H H H H 5-195 H H Me 2—(CH₂)₅-(4-iPrS-Ph) H H H H 5-196 H H Me 2 —(CH₂)₅-[3-(2-Et-PrS)-Ph] H HH H 5-197 H H Me 2 —(CH₂)₅-[4-(2-Et-PrS)-Ph] H H H H 5-198 H H Me 2—(CH₂)₅-(3-iBuS-Ph) H H H H 5-199 H H Me 2 —(CH₂)₅-(4-iBuS-Ph) H H H H5-200 H H Me 2 —(CH₂)₅-(3-cHx-Ph) H H H H 5-201 H H Me 2—(CH₂)₅-(4-cHx-Ph) H H H H 5-202 H H Me 2 —(CH₂)₅-(3-Ph-Ph) H H H H5-203 H H Me 2 —(CH₂)₅-(4-Ph-Ph) H H H H 5-204 H H Me 2—(CH₂)₅-(2,4-diMe-Ph) H H H H 5-205 H H Me 2 —(CH₂)₅-(3,4-diMe-Ph) H H HH 5-206 H H Me 2 —(CH₂)₅-(3,5-diMe-Ph) H H H H 5-207 H H Me 2—(CH₂)₅-Np(1) H H H H 5-208 H H Me 2 —(CH₂)₅-Np(2) H H H H 5-209 H H Me2 —(CH₂)₆-cPn H H H H 5-210 H H Me 2 —(CH₂)₆-cHx H H H H 5-211 H H Me 2—(CH₂)₆-cHx Me H H H 5-212 H H Me 2 —(CH₂)₆-cHx H Me H H 5-213 H H Me 2—(CH₂)₆-cHx F H H H 5-214 H H Me 2 —(CH₂)₆-cHx H F H H 5-215 H Me Me 2—(CH₂)₆-cHx H H H H 5-216 CO₂Me H Me 2 —(CH₂)₆-cHx H H H H 5-217 CO₂Et HMe 2 —(CH₂)₆-cHx H H H H 5-218 H H Me 2 —(CH₂)₆-(3-F-cHx) H H H H 5-219H H Me 2 —(CH₂)₆-(4-F-cHx) H H H H 5-220 H H Me 2 —(CH₂)₆-(4-Cl-cHx) H HH H 5-221 H H Me 2 —(CH₂)₆-(4-Br-cHx) H H H H 5-222 H H Me 2—(CH₂)₆-(3-Me-cHx) H H H H 5-223 H H Me 2 —(CH₂)₆-(4-Me-cHx) H H H H5-224 H H Me 2 —(CH₂)₆-(3-Et-cHx) H H H H 5-225 H H Me 2—(CH₂)₆-(4-Et-cHx) H H H H 5-226 H H Me 2 —(CH₂)₆-(3-Pr-cHx) H H H H5-227 H H Me 2 —(CH₂)₆-(4-Pr-cHx) H H H H 5-228 H H Me 2—(CH₂)₆-(4-iPr-cHx) H H H H 5-229 H H Me 2 —(CH₂)₆-(3-Bu-cHx) H H H H5-230 H H Me 2 —(CH₂)₆-(4-Bu-cHx) H H H H 5-231 H H Me 2—(CH₂)₆-(3-CF₃-cHx) H H H H 5-232 H H Me 2 —(CH₂)₆-(4-CF₃-cHx) H H H H5-233 H H Me 2 —(CH₂)₆-(3-MeO-cHx) H H H H 5-234 H H Me 2—(CH₂)₆-(4-MeO-cHx) H H H H 5-235 H H Me 2 —(CH₂)₆-(3-EtO-cHx) H H H H5-236 H H Me 2 —(CH₂)₆-(4-EtO-cHx) H H H H 5-237 H H Me 2—(CH₂)₆-(3-PrO-cHx) H H H H 5-238 H H Me 2 —(CH₂)₆-(4-PrO-cHx) H H H H5-239 H H Me 2 —(CH₂)₆-(3-iPrO-cHx) H H H H 5-240 H H Me 2—(CH₂)₆-(4-iPrO-cHx) H H H H 5-241 H H Me 2 —(CH₂)₆-[3-(2-Et-PrO)-cHx] HH H H 5-242 H H Me 2 —(CH₂)₆-[4-(2-Et-PrO)-cHx] H H H H 5-243 H H Me 2—(CH₂)₆-(3-iBuO-cHx) H H H H 5-244 H H Me 2 —(CH₂)₆-(4-iBuO-cHx) H H H H5-245 H H Me 2 —(CH₂)₆-(3-MeS-cHx) H H H H 5-246 H H Me 2—(CH₂)₆-(4-MeS-cHx) H H H H 5-247 H H Me 2 —(CH₂)₆-(3-EtS-cHx) H H H H5-248 H H Me 2 —(CH₂)₆-(4-EtS-cHx) H H H H 5-249 H H Me 2—(CH₂)₆-(3-PrS-cHx) H H H H 5-250 H H Me 2 —(CH₂)₆-(4-PrS-cHx) H H H H5-251 H H Me 2 —(CH₂)₆-(3-iPrS-cHx) H H H H 5-252 H H Me 2—(CH₂)₆-(4-iPrS-cHx) H H H H 5-253 H H Me 2 —(CH₂)₆-[3-(2-Et-PrS)-cHx] HH H H 5-254 H H Me 2 —(CH₂)₆-[4-(2-Et-PrS)-cHx] H H H H 5-255 H H Me 2—(CH₂)₆-(3-iBuS-cHx) H H H H 5-256 H H Me 2 —(CH₂)₆-(4-iBuS-cHx) H H H H5-257 H H Me 2 —(CH₂)₆-(3-cHx-cHx) H H H H 5-258 H H Me 2—(CH₂)₆-(4-cHx-cHx) H H H H 5-259 H H Me 2 —(CH₂)₆-(3-Ph-cHx) H H H H5-260 H H Me 2 —(CH₂)₆-(4-Ph-cHx) H H H H 5-261 H H Me 2—(CH₂)₆-(2,4-diMe-cHx) H H H H 5-262 H H Me 2 —(CH₂)₆-(3,4-diMe-cHx) H HH H 5-263 H H Me 2 —(CH₂)₆-(3,5-diMe-cHx) H H H H 5-264 H H Me 2—(CH₂)₆-Ph H H H H 5-265 H H Me 2 —(CH₂)₆-Ph Me H H H 5-266 H H Me 2—(CH₂)₆-Ph H Me H H 5-267 H H Me 2 —(CH₂)₆-Ph F H H H 5-268 H H Me 2—(CH₂)₆-Ph H F H H 5-269 H Me Me 2 —(CH₂)₆-Ph H H H H 5-270 CO₂Me H Me 2—(CH₂)₆-Ph H H H H 5-271 CO₂Et H Me 2 —(CH₂)₆-Ph H H H H 5-272 H H Me 2—(CH₂)₆-(3-F-Ph) H H H H 5-273 H H Me 2 —(CH₂)₆-(4-F-Ph) H H H H 5-274 HH Me 2 —(CH₂)₆-(4-Cl-Ph) H H H H 5-275 H H Me 2 —(CH₂)₆-(4-Br-Ph) H H HH 5-276 H H Me 2 —(CH₂)₆-(3-Me-Ph) H H H H 5-277 H H Me 2—(CH₂)₆-(4-Me-Ph) H H H H 5-278 H H Me 2 —(CH₂)₆-(3-Et-Ph) H H H H 5-279H H Me 2 —(CH₂)₆-(4-Et-Ph) H H H H 5-280 H H Me 2 —(CH₂)₆-(3-Pr-Ph) H HH H 5-281 H H Me 2 —(CH₂)₆-(4-Pr-Ph) H H H H 5-282 H H Me 2—(CH₂)₆-(3-iPr-Ph) H H H H 5-283 H H Me 2 —(CH₂)₆-(4-iPr-Ph) H H H H5-284 H H Me 2 —(CH₂)₆-(3-Bu-Ph) H H H H 5-285 H H Me 2—(CH₂)₆-(4-Bu-Ph) H H H H 5-286 H H Me 2 —(CH₂)₆-(3-CF₃-Ph) H H H H5-287 H H Me 2 —(CH₂)₆-(4-CF₃-Ph) H H H H 5-288 H H Me 2—(CH₂)₆-(3-MeO-Ph) H H H H 5-289 H H Me 2 —(CH₂)₆-(4-MeO-Ph) H H H H5-290 H H Me 2 —(CH₂)₆-(3-EtO-Ph) H H H H 5-291 H H Me 2—(CH₂)₆-(4-EtO-Ph) H H H H 5-292 H H Me 2 —(CH₂)₆-(3-PrO-Ph) H H H H5-293 H H Me 2 —(CH₂)₆-(4-PrO-Ph) H H H H 5-294 H H Me 2—(CH₂)₆-(3-iPrO-Ph) H H H H 5-295 H H Me 2 —(CH₂)₆-(4-iPrO-Ph) H H H H5-296 H H Me 2 —(CH₂)₆-[3-(2-Et-PrO)-Ph] H H H H 5-297 H H Me 2—(CH₂)₆-[4-(2-Et-PrO)-Ph] H H H H 5-298 H H Me 2 —(CH₂)₆-(3-iBuO-Ph) H HH H 5-299 H H Me 2 —(CH₂)₆-(4-iBuO-Ph) H H H H 5-300 H H Me 2—(CH₂)₆-(3-MeS-Ph) H H H H 5-301 H H Me 2 —(CH₂)₆-(4-MeS-Ph) H H H H5-302 H H Me 2 —(CH₂)₆-(3-EtS-Ph) H H H H 5-303 H H Me 2—(CH₂)₆-(4-EtS-Ph) H H H H 5-304 H H Me 2 —(CH₂)₆-(3-PrS-Ph) H H H H5-305 H H Me 2 —(CH₂)₆-(4-PrS-Ph) H H H H 5-306 H H Me 2—(CH₂)₆-(3-iPrS-Ph) H H H H 5-307 H H Me 2 —(CH₂)₆-(4-iPrS-Ph) H H H H5-308 H H Me 2 —(CH₂)₆-[3-(2-Et-PrS)-Ph] H H H H 5-309 H H Me 2—(CH₂)₆-[4-(2-Et-PrS)-Ph] H H H H 5-310 H H Me 2 —(CH₂)₆-(3-iBuS-Ph) H HH H 5-311 H H Me 2 —(CH₂)₆-(4-iBuS-Ph) H H H H 5-312 H H Me 2—(CH₂)₆-(3-cHx-Ph) H H H H 5-313 H H Me 2 —(CH₂)₆-(4-cHx-Ph) H H H H5-314 H H Me 2 —(CH₂)₆-(3-Ph-Ph) H H H H 5-315 H H Me 2—(CH₂)₆-(4-Ph-Ph) H H H H 5-316 H H Me 2 —(CH₂)₆-(2,4-diMe-Ph) H H H H5-317 H H Me 2 —(CH₂)₆-(3,4-diMe-Ph) H H H H 5-318 H H Me 2—(CH₂)₆-(3,5-diMe-Ph) H H H H 5-319 H H Me 2 —(CH₂)₆-Np(1) H H H H 5-320H H Me 2 —(CH₂)₆-Np(2) H H H H 5-321 H H Me 2 —(CH₂)-₇-cHx H H H H 5-322H H Me 2 —(CH₂)-₇-cHx H H H H 5-323 CO₂Me H Me 2 —(CH₂)₇-cHx H H H H5-324 CO₂Et H Me 2 —(CH₂)₇-cHx H H H H 5-325 H H Me 2 —(CH₂)₇-(4-F-cHx)H H H H 5-326 H H Me 2 —(CH₂)₇-(4-Me-cHx) H H H H 5-327 H H Me 2—(CH₂)₇-(4-Et-cHx) H H H H 5-328 H H Me 2 —(CH₂)₇-(4-CF₃-cHx) H H H H5-329 H H Me 2 —(CH₂)₇-(4-MeO-cHx) H H H H 5-330 H H Me 2—(CH₂)₇-(4-EtO-cHx) H H H H 5 331 H H Me 2 —(CH₂)₇-(4-MeS-cHx) H H H H5-332 H H Me 2 —(CH₂)₇-(4-cHx-cHx) H H H H 5-333 H H Me 2—(CH₂)₇-(4-Ph-cHx) H H H H 5-334 H H Me 2 —(CH₂)₇-Ph H H H H 5-335 H MeMe 2 —(CH₂)₇-Ph H H H H 5-336 CO₂Me H Me 2 —(CH₂)₇-Ph H H H H 5-337CO₂Et H Me 2 —(CH₂)₇-Ph H H H H 5-338 H H Me 2 —(CH₂)₇-(4-F-Ph) H H H H5-339 H H Me 2 —(CH₂)₇-(4-Me-Ph) H H H H 5-340 H H Me 2—(CH₂)₇-(4-Et-Ph) H H H H 5-341 H H Me 2 —(CH₂)₇-(4-CF₃-Ph) H H H H5-342 H H Me 2 —(CH₂)₇-(4-MeO-Ph) H H H H 5-343 H H Me 2—(CH₂)₇-(4-EtO-Ph) H H H H 5-344 H H Me 2 —(CH₂)₇-(4-MeS-Ph) H H H H5-345 H H Me 2 —(CH₂)₇-(4-cHx-Ph) H H H H 5-346 H H Me 2—(CH₂)₇-(4-Ph-Ph) H H H H 5-347 H H Me 2 —(CH₂)₈-cHx H H H H 5-348 H MeMe 2 —(CH₂)₈-cHx H H H H 5-349 CO₂Me H Me 2 —(CH₂)₈-cHx H H H H 5-350CO₂Et H Me 2 —(CH₂)₈-cHx H H H H 5-351 H H Me 2 —(CH₂)₈-(4-F-cHx) H H HH 5-352 H H Me 2 —(CH₂)₈-(4-Me-cHx) H H H H 5-353 H H Me 2—(CH₂)₈-(4-Et-cHx) H H H H 5-354 H H Me 2 —(CH₂)₈-(4-CF₃-cHx) H H H H5-355 H H Me 2 —(CH₂)₈-(4-MeO-cHx) H H H H 5-356 H H Me 2—(CH₂)₈-(4-EtO-cHx) H H H H 5-357 H H Me 2 —(CH₂)₈-(4-MeS-cHx) H H H H5-358 H H Me 2 —(CH₂)₈-(4-cHx-cHx) H H H H 5-359 H H Me 2—(CH₂)₈-(4-Ph-cHx) H H H H 5-360 H H Me 2 —(CH₂)₈-Ph H H H H 5-361 H MeMe 2 —(CH₂)₈-Ph H H H H 5-362 CO₂Me H Me 2 —(CH₂)₈-Ph H H H H 5-363CO₂Et H Me 2 —(CH₂)₈-Ph H H H H 5-364 H H Me 2 —(CH₂)₈-(4-F-Ph) H H H H5-365 H H Me 2 —(CH₂)₈-(4-Me-Ph) H H H H 5-366 H H Me 2—(CH₂)₈-(4-Et-Ph) H H H H 5-367 H H Me 2 —(CH₂)₈-(4-CF₃-Ph) H H H H5-368 H H Me 2 —(CH₂)₈-(4-MeO-Ph) H H H H 5-369 H H Me 2—(CH₂)₈-(4-EtO-Ph) H H H H 5-370 H H Me 2 —(CH₂)₈-(4-MeS-Ph) H H H H5-371 H H Me 2 —(CH₂)₈-(4-cHx-Ph) H H H H 5-372 H H Me 2—(CH₂)₈-(4-Ph-Ph) H H H H 5-373 H H Me 2 —(CH₂)₃—O-cHx H H H H 5-374 HMe Me 2 —(CH₂)₃—O-cHx H H H H 5-375 CO₂Me H Me 2 —(CH₂)₃—O-cHx H H H H5-376 CO₂Et H Me 2 —(CH₂)₃—O-cHx H H H H 5-377 H H Me 2—(CH₂)₃—O-(4-F-cHx) H H H H 5-378 H H Me 2 —(CH₂)₃—O-(4-Me-cHx) H H H H5-379 H H Me 2 —(CH₂)₃—O-(4-Et-cHx) H H H H 5-380 H H Me 2—(CH₂)₃—O-(4-CF₃-cHx) H H H H 5-381 H H Me 2 —(CH₂)₃—O-(4-MeO-cHx) H H HH 5-382 H H Me 2 —(CH₂)₃—O-(4-EtO-cHx) H H H H 5-383 H H Me 2—(CH₂)₃—O-(4-MeS-cHx) H H H H 5-384 H H Me 2 —(CH₂)₃—O-(4-cHx-cHx) H H HH 5-385 H H Me 2 —(CH₂)₃—O-(4-Ph-cHx) H H H H 5-386 H H Me 2—(CH₂)₃—O-Ph H H H H 5-387 H Me Me 2 —(CH₂)₃—O-Ph H H H H 5-388 CO₂Me HMe 2 —(CH₂)₃—O-Ph H H H H 5-389 CO₂Et H Me 2 —(CH₂)₃—O-Ph H H H H 5-390H H Me 2 —(CH₂)₃—O-(4-F-Ph) H H H H 5-391 H H Me 2 —(CH₂)₃—O-(4-Me-Ph) HH H H 5-392 H H Me 2 —(CH₂)₃—O-(4-Et-Ph) H H H H 5-393 H H Me 2—(CH₂)₃—O-(4-CF₃-Ph) H H H H 5-394 H H Me 2 —(CH₂)₃—O-(4-MeO-Ph) H H H H5-395 H H Me 2 —(CH₂)₃—O-(4-EtO-Ph) H H H H 5-396 H H Me 2—(CH₂)₃—O-(4-MeS-Ph) H H H H 5-397 H H Me 2 —(CH₂)₃—O-(4-cHx-Ph) H H H H5-398 H H Me 2 —(CH₂)₃—O-(4-Ph-Ph) H H H H 5-399 H H Me 2 —(CH₂)₄—O-cPnH H H H 5-400 H H Me 2 —(CH₂)₄—O-cHx H H H H 5-401 H H Me 2—(CH₂)₄—O-cHx Me H H H 5-402 H H Me 2 —(CH₂)₄—O-cHx H Me H H 5-403 H HMe 2 —(CH₂)₄—O-cHx F H H H 5-404 H H Me 2 —(CH₂)₄—O-cHx H F H H 5-405 HMe Me 2 —(CH₂)₄—O-cHx H H H H 5-406 CO₂Me H Me 2 —(CH₂)₄—O-cHx H H H H5-407 CO₂Et H Me 2 —(CH₂)₄—O-cHx H H H H 5-408 H H Me 2—(CH₂)₄—O-(3-F-cHx) H H H H 5-409 H H Me 2 —(CH₂)₄—O-(4-F-cHx) H H H H5-410 H H Me 2 —(CH₂)₄—O-(4-Cl-cHx) H H H H 5-411 H H Me 2—(CH₂)₄—O-(4-Br-cHx) H H H H 5-412 H H Me 2 —(CH₂)₄—O-(3-Me-cHx) H H H H5-413 H H Me 2 —(CH₂)₄—O-(4-Me-cHx) H H H H 5-414 H H Me 2—(CH₂)₄—O-(3-Et-cHx) H H H H 5-415 H H Me 2 —(CH₂)₄—O-(4-Et-cHx) H H H H5-416 H H Me 2 —(CH₂)₄—O-(3-Pr-cHx) H H H H 5-417 H H Me 2—(CH₂)₄—O-(4-Pr-cHx) H H H H 5-418 H H Me 2 —(CH₂)₄—O-(4-iPr-cHx) H H HH 5-419 H H Me 2 —(CH₂)₄—O-(3-Bu-cHx) H H H H 5-420 H H Me 2—(CH₂)₄—O-(4-Bu-cHx) H H H H 5-421 H H Me 2 —(CH₂)₄—O-(3-CF₃-cHx) H H HH 5-422 H H Me 2 —(CH₂)₄—O-(4-CF₃-cHx) H H H H 5-423 H H Me 2—(CH₂)₄—O-(3-MeO-cHx) H H H H 5-424 H H Me 2 —(CH₂)₄—O-(4-MeO-cHx) H H HH 5-425 H H Me 2 —(CH₂)₄—O-(3-EtO-cHx) H H H H 5-426 H H Me 2—(CH₂)₄—O-(4-EtO-cHx) H H H H 5-427 H H Me 2 —(CH₂)₄—O-(3-PrO-cHx) H H HH 5-428 H H Me 2 —(CH₂)₄—O-(4-PrO-cHx) H H H H 5-429 H H Me 2—(CH₂)₄—O-(3-iPrO-cHx) H H H H 5-430 H H Me 2 —(CH₂)₄—O-(4-iPrO-cHx) H HH H 5-431 H H Me 2 —(CH₂)₄—O-[3-(2-Et-PrO)-cHx] H H H H 5-432 H H Me 2—(CH₂)₄—O-[4-(2-Et-PrO)-cHx] H H H H 5-433 H H Me 2—(CH₂)₄—O-(3-iBuO-cHx) H H H H 5-434 H H Me 2 —(CH₂)₄—O-(4-iBuO-cHx) H HH H 5-435 H H Me 2 —(CH₂)₄—O-(3-MeS-cHx) H H H H 5-436 H H Me 2—(CH₂)₄—O-(4-MeS-cHx) H H H H 5-437 H H Me 2 —(CH₂)₄—O-(3-EtS-cHx) H H HH 5-438 H H Me 2 —(CH₂)₄—O-(4-EtS-cHx) H H H H 5-439 H H Me 2—(CH₂)₄—O-(3-PrS-cHx) H H H H 5-440 H H Me 2 —(CH₂)₄—O-(4-PrS-cHx) H H HH 5-441 H H Me 2 —(CH₂)₄—O-(3-iPrS-cHx) H H H H 5-442 H H Me 2—(CH₂)₄—O-(4-iPrS-cHx) H H H H 5-443 H H Me 2—(CH₂)₄—O-[3-(2-Et-PrS)-cHx] H H H H 5-444 H H Me 2—(CH₂)₄—O-[4-(2-Et-PrS)-cHx] H H H H 5-445 H H Me 2—(CH₂)₄—O-(3-iBuS-cHx) H H H H 5-446 H H Me 2 —(CH₂)₄—O-(4-iBuS-cHx) H HH H 5-447 H H Me 2 —(CH₂)₄—O-(3-cHx-cHx) H H H H 5-448 H H Me 2—(CH₂)₄—O-(4-cHx-cHx) H H H H 5-449 H H Me 2 —(CH₂)₄—O-(3-Ph-cHx) H H HH 5-450 H H Me 2 —(CH₂)₄—O-(4-Ph-cHx) H H H H 5-451 H H Me 2—(CH₂)₄—O-(2,4-diMe-cHx) H H H H 5-452 H H Me 2 —(CH₂)₄—O-(3,4-diMe-cHx)H H H H 5-453 H H Me 2 —(CH₂)₄—O-(3,5-diMe-cHx) H H H H 5-454 H H Me 2—(CH₂)₄—O-Ph H H H H 5-455 H H Me 2 —(CH₂)₄—O-Ph Me H H H 5-456 H H Me 2—(CH₂)₄—O-Ph H Me H H 5-457 H H Me 2 —(CH₂)₄—O-Ph F H H H 5-458 H H Me 2—(CH₂)₄—O-Ph H F H H 5-459 H Me Me 2 —(CH₂)₄—O-Ph H H H H 5-460 CO₂Me HMe 2 —(CH₂)₄—O-Ph H H H H 5-461 CO₂Et H Me 2 —(CH₂)₄—O-Ph H H H H 5-462H H Me 2 —(CH₂)₄—O-(3-F-Ph) H H H H 5-463 H H Me 2 —(CH₂)₄—O-(4-F-Ph) HH H H 5-464 H H Me 2 —(CH₂)₄—O-(4-Cl-Ph) H H H H 5-465 H H Me 2—(CH₂)₄—O-(4-Br-Ph) H H H H 5-466 H H Me 2 —(CH₂)₄—O-(3-Me-Ph) H H H H5-467 H H Me 2 —(CH₂)₄—O-(4-Me-Ph) H H H H 5-468 H H Me 2—(CH₂)₄—O-(3-Et-Ph) H H H H 5-469 H H Me 2 —(CH₂)₄—O-(4-Et-Ph) H H H H5-470 H H Me 2 —(CH₂)₄—O-(3-Pr-Ph) H H H H 5-471 H H Me 2—(CH₂)₄—O-(4-Pr-Ph) H H H H 5-472 H H Me 2 —(CH₂)₄—O-(3-iPr-Ph) H H H H5-473 H H Me 2 —(CH₂)₄—O-(4-iPr-Ph) H H H H 5-474 H H Me 2—(CH₂)₄—O-(3-Bu-Ph) H H H H 5-475 H H Me 2 —(CH₂)₄—O-(4-Bu-Ph) H H H H5-476 H H Me 2 —(CH₂)₄—O-(3-CF₃-Ph) H H H H 5-477 H H Me 2—(CH₂)₄—O-(4-CF₃-Ph) H H H H 5-478 H H Me 2 —(CH₂)₄—O-(3-MeO-Ph) H H H H5-479 H H Me 2 —(CH₂)₄—O-(4-MeO-Ph) H H H H 5-480 H H Me 2—(CH₂)₄—O-(3-EtO-Ph) H H H H 5-481 H H Me 2 —(CH₂)₄—O-(4-EtO-Ph) H H H H5-482 H H Me 2 —(CH₂)₄—O-(3-PrO-Ph) H H H H 5-483 H H Me 2—(CH₂)₄—O-(4-PrO-Ph) H H H H 5-484 H H Me 2 —(CH₂)₄—O-(3-iPrO-Ph) H H HH 5-485 H H Me 2 —(CH₂)₄—O-(4-iPrO-Ph) H H H H 5-486 H H Me 2—(CH₂)₄—O-[3-(2-Et-PrO)-Ph] H H H H 5-487 H H Me 2—(CH₂)₄—O-[4-(2-Et-PrO)-Ph] H H H H 5-488 H H Me 2 —(CH₂)₄—O-(3-iBuO-Ph)H H H H 5-489 H H Me 2 —(CH₂)₄—O-(4-iBuO-Ph) H H H H 5-490 H H Me 2—(CH₂)₄—O-(3-MeS-Ph) H H H H 5-491 H H Me 2 —(CH₂)₄—O-(4-MeS-Ph) H H H H5-492 H H Me 2 —(CH₂)₄—O-(3-EtS-Ph) H H H H 5-493 H H Me 2—(CH₂)₄—O-(4-EtS-Ph) H H H H 5-494 H H Me 2 —(CH₂)₄—O-(3-PrS-Ph) H H H H5-495 H H Me 2 —(CH₂)₄—O-(4-PrS-Ph) H H H H 5-496 H H Me 2—(CH₂)₄—O-(3-iPrS-Ph) H H H H 5-497 H H Me 2 —(CH₂)₄—O-(4-iPrS-Ph) H H HH 5-498 H H Me 2 —(CH₂)₄—O-[3-(2-Et-PrS)-Ph] H H H H 5-499 H H Me 2—(CH₂)₄—O-[4-(2-Et-PrS)-Ph] H H H H 5-500 H H Me 2 —(CH₂)₄—O-(3-iBuS-Ph)H H H H 5-501 H H Me 2 —(CH₂)₄—O-(4-iBuS-Ph) H H H H 5-502 H H Me 2—(CH₂)₄—O-(3-cHx-Ph) H H H H 5-503 H H Me 2 —(CH₂)₄—O-(4-cHx-Ph) H H H H5-504 H H Me 2 —(CH₂)₄—O-(3-Ph-Ph) H H H H 5-505 H H Me 2—(CH₂)₄—O-(4-Ph-Ph) H H H H 5-506 H H Me 2 —(CH₂)₄—O-(2,4-diMe-Ph) H H HH 5-507 H H Me 2 —(CH₂)₄—O-(3,4-diMe-Ph) H H H H 5-508 H H Me 2—(CH₂)₄—O-(3,5-diMe-Ph) H H H H 5-509 H H Me 2 —(CH₂)₅—O-cHx H H H H5-510 H H Me 2 —(CH₂)₅—O-Ph H H H H 5-511 H H Me 2 —(CH₂)₆—O-cHx H H H H5-512 H H Me 2 —(CH₂)₆—O-Ph H H H H 5-513 H H Me 2 —(CH₂)₃—OCH₂-cHx H HH H 5-514 H Me Me 2 —(CH₂)₃—OCH₂-cHx H H H H 5-515 CO₂Me H Me 2—(CH₂)₃—OCH₂-cHx H H H H 5-516 CO₂Et H Me 2 —(CH₂)₃—OCH₂-cHx H H H H5-517 H H Me 2 —(CH₂)₃—OCH₂-(4-F-cHx) H H H H 5-518 H H Me 2—(CH₂)₃—OCH₂-(4-Me-cHx) H H H H 5-519 H H Me 2 —(CH₂)₃—OCH₂-(4-Et-cHx) HH H H 5-520 H H Me 2 —(CH₂)₃—OCH₂-(4-CF₃-cHx) H H H H 5-521 H H Me 2—(CH₂)₃—OCH₂-(4-MeO-cHx) H H H H 5-522 H H Me 2 —(CH₂)₃—OCH₂-(4-EtO-cHx)H H H H 5-523 H H Me 2 —(CH₂)₃—OCH₂-(4-MeS-cHx) H H H H 5-524 H H Me 2—(CH₂)₃—OCH₂-(4-cHx-cHx) H H H H 5-525 H H Me 2 —(CH₂)₃—OCH₂-(4-Ph-cHx)H H H H 5-526 H H Me 2 —(CH₂)₃—OCH₂-Ph H H H H 5-527 H Me Me 2—(CH₂)₃—OCH₂-Ph H H H H 5-528 CO₂Me H Me 2 —(CH₂)₃—OCH₂-Ph H H H H 5-529CO₂Et H Me 2 —(CH₂)₃—OCH₂-Ph H H H H 5-530 H H Me 2—(CH₂)₃—OCH₂-(4-F-Ph) H H H H 5-531 H H Me 2 —(CH₂)₃—OCH₂-(4-Me-Ph) H HH H 5-532 H H Me 2 —(CH₂)₃—OCH₂-(4-Et-Ph) H H H H 5-533 H H Me 2—(CH₂)₃—OCH₂-(4-CF₃-Ph) H H H H 5-534 H H Me 2 —(CH₂)₃—OCH₂-(4-MeO-Ph) HH H H 5-535 H H Me 2 —(CH₂)₃—OCH₂-(4-EtO-Ph) H H H H 5-536 H H Me 2—(CH₂)₃—OCH₂-(4-MeS-Ph) H H H H 5-537 H H Me 2 —(CH₂)₃—OCH₂-(4-cHx-Ph) HH H H 5-538 H H Me 2 —(CH₂)₃—OCH₂-(4-Ph-Ph) H H H H 5-539 H H Me 2—(CH₂)₄—OCH₂-cPn H H H H 5-540 H H Me 2 —(CH₂)₄—OCH₂-cHx H H H H 5-541 HH Me 2 —(CH₂)₄—OCH₂-cHx Me H H H 5-542 H H Me 2 —(CH₂)₄—OCH₂-cHx H Me HH 5-543 H H Me 2 —(CH₂)₄—OCH₂-cHx F H H H 5-544 H H Me 2—(CH₂)₄—OCH₂-cHx H F H H 5-545 H Me Me 2 —(CH₂)₄—OCH₂-cHx H H H H 5-546CO₂Me H Me 2 —(CH₂)₄—OCH₂-cHx H H H H 5-547 CO₂Et H Me 2—(CH₂)₄—OCH₂-cHx H H H H 5-548 H H Me 2 —(CH₂)₄—OCH₂-(3-F-cHx) H H H H5-549 H H Me 2 —(CH₂)₄—OCH₂-(4-F-cHx) H H H H 5-550 H H Me 2—(CH₂)₄—OCH₂-(4-Cl-cHx) H H H H 5-551 H H Me 2 —(CH₂)₄—OCH₂-(4-Br-cHx) HH H H 5-552 H H Me 2 —(CH₂)₄—OCH₂-(3-Me-cHx) H H H H 5-553 H H Me 2—(CH₂)₄—OCH₂-(4-Me-cHx) H H H H 5-554 H H Me 2 —(CH₂)₄—OCH₂-(3-Et-cHx) HH H H 5-555 H H Me 2 —(CH₂)₄—OCH₂-(4-Et-cHx) H H H H 5-556 H H Me 2—(CH₂)₄—OCH₂-(3-Pr-cHx) H H H H 5-557 H H Me 2 —(CH₂)₄—OCH₂-(4-Pr-cHx) HH H H 5-558 H H Me 2 —(CH₂)₄—OCH₂-(4-iPr-cHx) H H H H 5-559 H H Me 2—(CH₂)₄—OCH₂-(3-Bu-cHx) H H H H 5-560 H H Me 2 —(CH₂)₄—OCH₂-(4-Bu-cHx) HH H H 5-561 H H Me 2 —(CH₂)₄—OCH₂-(3-CF₃-cHx) H H H H 5-562 H H Me 2—(CH₂)₄—OCH₂-(4-CF₃-cHx) H H H H 5-563 H H Me 2 —(CH₂)₄—OCH₂-(3-MeO-cHx)H H H H 5-564 H H Me 2 —(CH₂)₄—OCH₂-(4-MeO-cHx) H H H H 5-565 H H Me 2—(CH₂)₄—OCH₂-(3-EtO-cHx) H H H H 5-566 H H Me 2 —(CH₂)₄—OCH₂-(4-EtO-cHx)H H H H 5-567 H H Me 2 —(CH₂)₄—OCH₂-(3-PrO-cHx) H H H H 5-568 H H Me 2—(CH₂)₄—OCH₂-(4-PrO-cHx) H H H H 5-569 H H Me 2—(CH₂)₄—OCH₂-(3-iPrO-cHx) H H H H 5-570 H H Me 2—(CH₂)₄—OCH₂-(4-iPrO-cHx) H H H H 5-571 H H Me 2—(CH₂)₄—OCH₂-[3-(2-Et-PrO)-cHx] H H H H 5-572 H H Me 2—(CH₂)₄—OCH₂-[4-(2-Et-PrO)-cHx] H H H H 5-573 H H Me 2—(CH₂)₄—OCH₂-(3-iBuO-cHx) H H H H 5-574 H H Me 2—(CH₂)₄—OCH₂-(4-iBuO-cHx) H H H H 5-575 H H Me 2—(CH₂)₄—OCH₂-(3-MeS-cHx) H H H H 5-576 H H Me 2 —(CH₂)₄—OCH₂-(4-MeS-cHx)H H H H 5-577 H H Me 2 —(CH₂)₄—OCH₂-(3-EtS-cHx) H H H H 5-578 H H Me 2—(CH₂)₄—OCH₂-(4-EtS-cHx) H H H H 5-579 H H Me 2 —(CH₂)₄—OCH₂-(3-PrS-cHx)H H H H 5-580 H H Me 2 —(CH₂)₄—OCH₂-(4-PrS-cHx) H H H H 5-581 H H Me 2—(CH₂)₄—OCH₂-(3-iPrS-cHx) H H H H 5-582 H H Me 2—(CH₂)₄—OCH₂-(4-iPrS-cHx) H H H H 5-583 H H Me 2—(CH₂)₄—OCH₂-[3-(2-Et-PrS)-cHx] H H H H 5-584 H H Me 2—(CH₂)₄—OCH₂-[4-(2-Et-PrS)-cHx] H H H H 5-585 H H Me 2—(CH₂)₄—OCH₂-(3-iBuS-cHx) H H H H 5-586 H H Me 2—(CH₂)₄—OCH₂-(4-iBuS-cHx) H H H H 5-587 H H Me 2—(CH₂)₄—OCH₂-(3-cHx-cHx) H H H H 5-588 H H Me 2 —(CH₂)₄—OCH₂-(4-cHx-cHx)H H H H 5-589 H H Me 2 —(CH₂)₄—OCH₂-(3-Ph-cHx) H H H H 5-590 H H Me 2—(CH₂)₄—OCH₂-(4-Ph-cHx) H H H H 5-591 H H Me 2—(CH₂)₄—OCH₂-(2,4-diMe-cHx) H H H H 5-592 H H Me 2—(CH₂)₄—OCH₂-(3,4-diMe-cHx) H H H H 5-593 H H Me 2—(CH₂)₄—OCH₂-(3,5-diMe-cHx) H H H H 5-594 H H Me 2 —(CH₂)₄—OCH₂-Ph H H HH 5-595 H H Me 2 —(CH₂)₄—OCH₂-Ph Me H H H 5-596 H H Me 2 —(CH₂)₄—OCH₂-PhH Me H H 5-597 H H Me 2 —(CH₂)₄—OCH₂-Ph F H H H 5-598 H H Me 2—(CH₂)₄—OCH₂-Ph H F H H 5-599 H Me Me 2 —(CH₂)₄—OCH₂-Ph H H H H 5-600CO₂Me H Me 2 —(CH₂)₄—OCH₂-Ph H H H H 5-601 CO₂Et H Me 2 —(CH₂)₄—OCH₂-PhH H H H 5-602 H H Me 2 —(CH₂)₄—OCH₂-(3-F-Ph) H H H H 5-603 H H Me 2—(CH₂)₄—OCH₂-(4-F-Ph) H H H H 5-604 H H Me 2 —(CH₂)₄—OCH₂-(4-Cl-Ph) H HH H 5-605 H H Me 2 —(CH₂)₄—OCH₂-(4-Br-Ph) H H H H 5-606 H H Me 2—(CH₂)₄—OCH₂-(3-Me-Ph) H H H H 5-607 H H Me 2 —(CH₂)₄—OCH₂-(4-Me-Ph) H HH H 5-608 H H Me 2 —(CH₂)₄—OCH₂-(3-Et-Ph) H H H H 5-609 H H Me 2—(CH₂)₄—OCH₂-(4-Et-Ph) H H H H 5-610 H H Me 2 —(CH₂)₄—OCH₂-(3-Pr-Ph) H HH H 5-611 H H Me 2 —(CH₂)₄—OCH₂-(4-Pr-Ph) H H H H 5-612 H H Me 2—(CH₂)₄—OCH₂-(3-iPr-Ph) H H H H 5-613 H H Me 2 —(CH₂)₄—OCH₂-(4-iPr-Ph) HH H H 5-614 H H Me 2 —(CH₂)₄—OCH₂-(3-Bu-Ph) H H H H 5-615 H H Me 2—(CH₂)₄—OCH₂-(4-Bu-Ph) H H H H 5-616 H H Me 2 —(CH₂)₄—OCH₂-(3-CF₃-Ph) HH H H 5-617 H H Me 2 —(CH₂)₄—OCH₂-(4-CF₃-Ph) H H H H 5-618 H H Me 2—(CH₂)₄—OCH₂-(3-MeO-Ph) H H H H 5-619 H H Me 2 —(CH₂)₄—OCH₂-(4-MeO-Ph) HH H H 5-620 H H Me 2 —(CH₂)₄—OCH₂-(3-EtO-Ph) H H H H 5-621 H H Me 2—(CH₂)₄—OCH₂-(4-EtO-Ph) H H H H 5-622 H H Me 2 —(CH₂)₄—OCH₂-(3-PrO-Ph) HH H H 5-623 H H Me 2 —(CH₂)₄—OCH₂-(4-PrO-Ph) H H H H 5-624 H H Me 2—(CH₂)₄—OCH₂-(3-iPrO-Ph) H H H H 5-625 H H Me 2 —(CH₂)₄—OCH₂-(4-iPrO-Ph)H H H H 5-626 H H Me 2 —(CH₂)₄—OCH₂-[3-(2-Et-PrO)-Ph] H H H H 5-627 H HMe 2 —(CH₂)₄—OCH₂-[4-(2-Et-PrO)-Ph] H H H H 5-628 H H Me 2—(CH₂)₄—OCH₂-(3-iBuO-Ph) H H H H 5-629 H H Me 2 —(CH₂)₄—OCH₂-(4-iBuO-Ph)H H H H 5-630 H H Me 2 —(CH₂)₄—OCH₂-(3-MeS-Ph) H H H H 5-631 H H Me 2—(CH₂)₄—OCH₂-(4-MeS-Ph) H H H H 5-632 H H Me 2 —(CH₂)₄—OCH₂-(3-EtS-Ph) HH H H 5-633 H H Me 2 —(CH₂)₄—OCH₂-(4-EtS-Ph) H H H H 5-634 H H Me 2—(CH₂)₄—OCH₂-(3-PrS-Ph) H H H H 5-635 H H Me 2 —(CH₂)₄—OCH₂-(4-PrS-Ph) HH H H 5-636 H H Me 2 —(CH₂)₄—OCH₂-(3-iPrS-Ph) H H H H 5-637 H H Me 2—(CH₂)₄—OCH₂-(4-iPrS-Ph) H H H H 5-638 H H Me 2—(CH₂)₄—OCH₂-[3-(2-Et-PrS)-Ph] H H H H 5-639 H H Me 2—(CH₂)₄—OCH₂-[4-(2-Et-PrS)-Ph] H H H H 5-640 H H Me 2—(CH₂)₄—OCH₂-(3-iBuS-Ph) H H H H 5-641 H H Me 2 —(CH₂)₄—OCH₂-(4-iBuS-Ph)H H H H 5-642 H H Me 2 —(CH₂)₄—OCH₂-(3-cHx-Ph) H H H H 5-643 H H Me 2—(CH₂)₄—OCH₂-(4-cHx-Ph) H H H H 5-644 H H Me 2 —(CH₂)₄—OCH₂-(3-Ph-Ph) HH H H 5-645 H H Me 2 —(CH₂)₄—OCH₂-(4-Ph-Ph) H H H H 5-646 H H Me 2—(CH₂)₄—OCH₂-(2,4-diMe-Ph) H H H H 5-647 H H Me 2—(CH₂)₄—OCH₂-(3,4-diMe-Ph) H H H H 5-648 H H Me 2—(CH₂)₄—OCH₂-(3,5-diMe-Ph) H H H H 5-649 H H Me 2 —(CH₂)₅—OCH₂-cHx H H HH 5-650 H H Me 2 —(CH₂)₅—OCH₂-Ph H H H H 5-651 H H Me 2 —(CH₂)₆—OCH₂-cHxH H H H 5-652 H H Me 2 —(CH₂)₆—OCH₂-Ph H H H H 5-653 H H Me 2 —CH═CH-cHxH H H H 5-654 H H Me 2 —CH═CH-Ph H H H H 5-655 H H Me 2—CH═CH—(CH₂)₂-cHx H H H H 5-656 H H Me 2 —CH═CH—(CH₂)₂-Ph H H H H 5-657H H Me 2 —CH═CH—(CH₂)₃-cHx H H H H 5-658 H Me Me 2 —CH═CH—(CH₂)₃-cHx H HH H 5-659 CO₂Me H Me 2 —CH═CH—(CH₂)₃-cHx H H H H 5-660 CO₂Et H Me 2—CH═CH—(CH₂)₃-cHx H H H H 5-661 H H Me 2 —CH═CH—(CH₂)₃-(4-F-cHx) H H H H5-662 H H Me 2 —CH═CH—(CH₂)₃-(4-Me-cHx) H H H H 5-663 H H Me 2—CH═CH—(CH₂)₃-(4-Et-cHx) H H H H 5-664 H H Me 2—CH═CH—(CH₂)₃-(4-CF₃-cHx) H H H H 5-665 H H Me 2—CH═CH—(CH₂)₃-(4-MeO-cHx) H H H H 5-666 H H Me 2—CH═CH—(CH₂)₃-(4-EtO-cHx) H H H H 5-667 H H Me 2—CH═CH—(CH₂)₃-(4-MeS-cHx) H H H H 5-668 H H Me 2—CH═CH—(CH₂)₃-(4-cHx-cHx) H H H H 5-669 H H Me 2—CH═CH—(CH₂)₃-(4-Ph-cHx) H H H H 5-670 H H Me 2 —CH═CH—(CH₂)₃-Ph H H H H5-671 H Me Me 2 —CH═CH—(CH₂)₃-Ph H H H H 5-672 CO₂Me H Me 2—CH═CH—(CH₂)₃-Ph H H H H 5-673 CO₂Et H Me 2 —CH═CH—(CH₂)₃-Ph H H H H5-674 H H Me 2 —CH═CH—(CH₂)₃-(4-F-Ph) H H H H 5-675 H H Me 2—CH═CH—(CH₂)₃-(4-Me-Ph) H H H H 5-676 H H Me 2 —CH═CH—(CH₂)₃-(4-Et-Ph) HH H H 5-677 H H Me 2 —CH═CH—(CH₂)₃-(4-CF₃-Ph) H H H H 5-678 H H Me 2—CH═CH—(CH₂)₃-(4-MeO-Ph) H H H H 5-679 H H Me 2 —CH═CH—(CH₂)₃-(4-EtO-Ph)H H H H 5-680 H H Me 2 —CH═CH—(CH₂)₃-(4-MeS-Ph) H H H H 5-681 H H Me 2—CH═CH—(CH₂)₃-(4-cHx-Ph) H H H H 5-682 H H Me 2 —CH═CH—(CH₂)₃-(4-Ph-Ph)H H H H 5-683 H H Me 2 —CH═CH—(CH₂)₄-cHx H H H H 5-684 H Me Me 2—CH═CH—(CH₂)₄-cHx H H H H 5-685 CO₂Me H Me 2 —CH═CH—(CH₂)₄-cHx H H H H5-686 CO₂Et H Me 2 —CH═CH—(CH₂)₄-cHx H H H H 5-687 H H Me 2—CH═CH—(CH₂)₄-(4-F-cHx) H H H H 5-688 H H Me 2 —CH═CH—(CH₂)₄-(4-Me-cHx)H H H H 5-689 H H Me 2 —CH═CH—(CH₂)₄-(4-Et-cHx) H H H H 5-690 H H Me 2—CH═CH—(CH₂)₄-(4-CF₃-cHx) H H H H 5-691 H H Me 2—CH═CH—(CH₂)₄-(4-MeO-cHx) H H H H 5-692 H H Me 2—CH═CH—(CH₂)₄-(4-EtO-cHx) H H H H 5-693 H H Me 2—CH═CH—(CH₂)₄-(4-MeS-cHx) H H H H 5-694 H H Me 2—CH═CH—(CH₂)₄-(4-cHx-cHx) H H H H 5-695 H H Me 2—CH═CH—(CH₂)₄-(4-Ph-cHx) H H H H 5-696 H H Me 2 —CH═CH—(CH₂)₄-Ph H H H H5-697 H Me Me 2 —CH═CH—(CH₂)₄-Ph H H H H 5-698 CO₂Me H Me 2—CH═CH—(CH₂)₄-Ph H H H H 5-699 CO₂Et H Me 2 —CH═CH—(CH₂)₄-Ph H H H H5-700 H H Me 2 —CH═CH—(CH₂)₄-(4-F-Ph) H H H H 5-701 H H Me 2—CH═CH—(CH₂)₄-(4-Me-Ph) H H H H 5-702 H H Me 2 —CH═CH—(CH₂)₄-(4-Et-Ph) HH H H 5-703 H H Me 2 —CH═CH—(CH₂)₄-(4-CF₃-Ph) H H H H 5-704 H H Me 2—CH═CH—(CH₂)₄-(4-MeO-Ph) H H H H 5-705 H H Me 2 —CH═CH—(CH₂)₄-(4-EtO-Ph)H H H H 5-706 H H Me 2 —CH═CH—(CH₂)₄-(4-MeS-Ph) H H H H 5-707 H H Me 2—CH═CH—(CH₂)₄-(4-cHx-Ph) H H H H 5-708 H H Me 2 —CH═CH—(CH₂)₄-(4-Ph-Ph)H H H H 5-709 H H Me 2 —CH═CH—(CH₂)₅-cHx H H H H 5-710 H H Me 2—CH═CH—(CH₂)₅-Ph H H H H 5-711 H H Me 2 —CH═CH—(CH₂)₆-cHx H H H H 5-712H H Me 2 —CH═CH—(CH₂)₆-Ph H H H H 5-713 H H Me 2 —C═C—CH₂O-cHx H H H H5-714 H H Me 2 —C═C—CH₂O-Ph H H H H 5-715 H H Me 2 —C═C—(CH₂)₂O-cHx H HH H 5-716 H H Me 2 —C═C—(CH₂)₂O-Ph H H H H 5-717 H H Me 2 —C≡C-cHx H H HH 5-718 H Me Me 2 —C≡C-cHx H H H H 5-719 CO₂Me H Me 2 —C≡C-cHx H H H H5-720 CO₂Et H Me 2 —C≡C-cHx H H H H 5-721 H H Me 2 —C≡C-(4-F-cHx) H H HH 5-722 H H Me 2 —C≡C-(4-Me-cHx) H H H H 5-723 H H Me 2 —C≡C-(4-Et-cHx)H H H H 5-724 H H Me 2 —C≡C-(4-CF₃-cHx) H H H H 5-725 H H Me 2—C≡C-(4-MeO-cHx) H H H H 5-726 H H Me 2 —C≡C-(4-EtO-cHx) H H H H 5-727 HH Me 2 —C≡C-(4-MeS-cHx) H H H H 5-728 H H Me 2 —C≡C-(4-cHx-cHx) H H H H5-729 H H Me 2 —C≡C-(4-Ph-cHx) H H H H 5-730 H H Me 2 —C≡C-Ph H H H H5-731 H Me Me 2 —C≡C-Ph H H H H 5-732 CO₂Me H Me 2 —C≡C-Ph H H H H 5-733CO₂Et H Me 2 —C≡C-Ph H H H H 5-734 H H Me 2 —C≡C-(4-F-Ph) H H H H 5-735H H Me 2 —C≡C-(4-Me-Ph) H H H H 5-736 H H Me 2 —C≡C-(4-Pr-Ph) H H H H5-737 H H Me 2 —C≡C-(4-Bu-Ph) H H H H 5-738 H H Me 2 —C≡C-(4-MeO-Ph) H HH H 5-739 H H Me 2 —C≡C-(4-EtO-Ph) H H H H 5-740 H H Me 2—C≡C-(4-PrO-Ph) H H H H 5-741 H H Me 2 —C≡C-(4-cHx-Ph) H H H H 5 742 H HMe 2 —C≡C-(4-Ph-Ph) H H H H 5-743 H H Me 2 —C≡C—(CH₂)₂-cHx H H H H 5-744H Me Me 2 —C≡C—(CH₂)₂-cHx H H H H 5-745 CO₂Me H Me 2 —C≡C—(CH₂)₂-cHx H HH H 5-746 CO₂Et H Me 2 —C≡C—(CH₂)₂-cHx H H H H 5-747 H H Me 2—C≡C—(CH₂)₂-(4-F-cHx) H H H H 5-748 H H Me 2 —C≡C—(CH₂)₂-(4-Me-cHx) H HH H 5-749 H H Me 2 —C≡C—(CH₂)₂-(4-Et-cHx) H H H H 5-750 H H Me 2—C≡C—(CH₂)₂-(4-CF₃-cHx) H H H H 5-751 H H Me 2 —C≡C—(CH₂)₂-(4-MeO-cHx) HH H H 5-752 H H Me 2 —C≡C—(CH₂)₂-(4-EtO-cHx) H H H H 5-753 H H Me 2—C≡C—(CH₂)₂-(4-MeS-cHx) H H H H 5-754 H H Me 2 —C≡C—(CH₂)₂-(4-cHx-cHx) HH H H 5-755 H H Me 2 —C≡C—(CH₂)₂-(4-Ph-cHx) H H H H 5-756 H H Me 2—C≡C—(CH₂)₂-Ph H H H H 5-757 H Me Me 2 —C≡C—(CH₂)₂-Ph H H H H 5-758CO₂Me H Me 2 —C≡C—(CH₂)₂-Ph H H H H 5-759 CO₂Et H Me 2 —C≡C—(CH₂)₂-Ph HH H H 5-760 H H Me 2 —C≡C—(CH₂)₂-(4-F-Ph) H H H H 5-761 H H Me 2—C≡C—(CH₂)₂-(4-Me-Ph) H H H H 5-762 H H Me 2 —C≡C—(CH₂)₂-(4-Et-Ph) H H HH 5-763 H H Me 2 —C≡C—(CH₂)₂-(4-CF₃-Ph) H H H H 5-764 H H Me 2—C≡C—(CH₂)₂-(4-MeO-Ph) H H H H 5-765 H H Me 2 —C≡C—(CH₂)₂-(4-EtO-Ph) H HH H 5-766 H H Me 2 —C≡C—(CH₂)₂-(4-MeS-Ph) H H H H 5-767 H H Me 2—C≡C—(CH₂)₂-(4-cHx-Ph) H H H H 5-768 H H Me 2 —C≡C—(CH₂)₂-(4-Ph-Ph) H HH H 5-769 H H Me 2 —C≡C—(CH₂)₃-cPn H H H H 5-770 H H Me 2—C≡C—(CH₂)₃-cHx H H H H 5-771 H H Me 2 —C≡C—(CH₂)₃-cHx Me H H H 5-772 HH Me 2 —C≡C—(CH₂)₃-cHx H Me H H 5-773 H H Me 2 —C≡C—(CH₂)₃-cHx F H H H5-774 H H Me 2 —C≡C—(CH₂)₃-cHx H F H H 5-775 H Me Me 2 —C≡C—(CH₂)₃-cHx HH H H 5-776 CO₂Me H Me 2 —C≡C—(CH₂)₃-cHx H H H H 5-777 CO₂Et H Me 2—C≡C—(CH₂)₃-cHx H H H H 5-778 H H Me 2 —C≡C—(CH₂)₃-(3-F-cHx) H H H H5-779 H H Me 2 —C≡C—(CH₂)₃-(4-F-cHx) H H H H 5-780 H H Me 2—C≡C—(CH₂)₃-(4-Cl-cHx) H H H H 5-781 H H Me 2 —C≡C—(CH₂)₃-(4-Br-cHx) H HH H 5-782 H H Me 2 —C≡C—(CH₂)₃-(3-Me-cHx) H H H H 5-783 H H Me 2—C≡C—(CH₂)₃-(4-Me-cHx) H H H H 5-784 H H Me 2 —C≡C—(CH₂)₃-(3-Et-cHx) H HH H 5-785 H H Me 2 —C≡C—(CH₂)₃-(4-Et-cHx) H H H H 5-786 H H Me 2—C≡C—(CH₂)₃-(3-Pr-cHx) H H H H 5-787 H H Me 2 —C≡C—(CH₂)₃-(4-Pr-cHx) H HH H 5-788 H H Me 2 —C≡C—(CH₂)₃-(4-iPr-cHx) H H H H 5-789 H H Me 2—C≡C—(CH₂)₃-(3-Bu-cHx) H H H H 5-790 H H Me 2 —C≡C—(CH₂)₃-(4-Bu-cHx) H HH H 5-791 H H Me 2 —C≡C—(CH₂)₃-(3-CF₃-cHx) H H H H 5-792 H H Me 2—C≡C—(CH₂)₃-(4-CF₃-cHx) H H H H 5-793 H H Me 2 —C≡C—(CH₂)₃-(3-MeO-cHx) HH H H 5-794 H H Me 2 —C≡C—(CH₂)₃-(4-MeO-cHx) H H H H 5-795 H H Me 2—C≡C—(CH₂)₃-(3-EtO-cHx) H H H H 5-796 H H Me 2 —C≡C—(CH₂)₃-(4-EtO-cHx) HH H H 5-797 H H Me 2 —C≡C—(CH₂)₃-(3-PrO-cHx) H H H H 5-798 H H Me 2—C≡C—(CH₂)₃-(4-PrO-cHx) H H H H 5-799 H H Me 2 —C≡C—(CH₂)₃-(3-iPrO-cHx)H H H H 5-800 H H Me 2 —C≡C—(CH₂)₃-(4-iPrO-cHx) H H H H 5-801 H H Me 2—C≡C—(CH₂)₃-[3-(2-Et-PrO)-cHx] H H H H 5-802 H H Me 2—C≡C—(CH₂)₃-[4-(2-Et-PrO)-cHx] H H H H 5-803 H H Me 2—C≡C—(CH₂)₃-(3-iBuO-cHx) H H H H 5-804 H H Me 2 —C≡C—(CH₂)₃-(4-iBuO-cHx)H H H H 5-805 H H Me 2 —C≡C—(CH₂)₃-(3-MeS-cHx) H H H H 5-806 H H Me 2—C≡C—(CH₂)₃-(4-MeS-cHx) H H H H 5-807 H H Me 2 —C≡C—(CH₂)₃-(3-EtS-cHx) HH H H 5-808 H H Me 2 —C≡C—(CH₂)₃-(4-EtS-cHx) H H H H 5-809 H H Me 2—C≡C—(CH₂)₃-(3-PrS-cHx) H H H H 5-810 H H Me 2 —C≡C—(CH₂)₃-(4-PrS-cHx) HH H H 5-811 H H Me 2 —C≡C—(CH₂)₃-(3-iPrS-cHx) H H H H 5-812 H H Me 2—C≡C—(CH₂)₃-(4-iPrS-cHx) H H H H 5-813 H H Me 2—C≡C—(CH₂)₃-[3-(2-Et-PrS)-cHx] H H H H 5-814 H H Me 2—C≡C—(CH₂)₃-[4-(2-Et-PrS)-cHx] H H H H 5-815 H H Me 2—C≡C—(CH₂)₃-(3-iBuS-cHx) H H H H 5-816 H H Me 2 —C≡C—(CH₂)₃-(4-iBuS-cHx)H H H H 5-817 H H Me 2 —C≡C—(CH₂)₃-(3-cHx-cHx) H H H H 5-818 H H Me 2—C≡C—(CH₂)₃-(4-cHx-cHx) H H H H 5-819 H H Me 2 —C≡C—(CH₂)₃-(3-Ph-cHx) HH H H 5-820 H H Me 2 —C≡C—(CH₂)₃-(4-Ph-cHx) H H H H 5-821 H H Me 2—C≡C—(CH₂)₃-(2,4-diMe-cHx) H H H H 5-822 H H Me 2—C≡C—(CH₂)₃-(3,4-diMe-cHx) H H H H 5-823 H H Me 2—C≡C—(CH₂)₃-(3,5-diMe-cHx) H H H H 5-824 H H Me 2 —C≡C—(CH₂)₃-Ph H H H H5-825 H H Me 2 —C≡C—(CH₂)₃-Ph Me H H H 5-826 H H Me 2 —C≡C—(CH₂)₃-Ph HMe H H 5-827 H H Me 2 —C≡C—(CH₂)₃-Ph F H H H 5-828 H H Me 2—C≡C—(CH₂)₃-Ph H F H H 5-829 H Me Me 2 —C≡C—(CH₂)₃-Ph H H H H 5-830CO₂Me H Me 2 —C≡C—(CH₂)₃-Ph H H H H 5-831 CO₂Et H Me 2 —C≡C—(CH₂)₃-Ph HH H H 5-832 H H Me 2 —C≡C—(CH₂)₃-(3-F-Ph) H H H H 5-833 H H Me 2—C≡C—(CH₂)₃-(4-F-Ph) H H H H 5-834 H H Me 2 —C≡C—(CH₂)₃-(4-Cl-Ph) H H HH 5-835 H H Me 2 —C≡C—(CH₂)₃-(4-Br-Ph) H H H H 5-836 H H Me 2—C≡C—(CH₂)₃-(3-Me-Ph) H H H H 5-837 H H Me 2 —C≡C—(CH₂)₃-(4-Me-Ph) H H HH 5-838 H H Me 2 —C≡C—(CH₂)₃-(3-Et-Ph) H H H H 5-839 H H Me 2—C≡C—(CH₂)₃-(4-Et-Ph) H H H H 5-840 H H Me 2 —C≡C—(CH₂)₃-(3-Pr-Ph) H H HH 5-841 H H Me 2 —C≡C—(CH₂)₃-(4-Pr-Ph) H H H H 5-842 H H Me 2—C≡C—(CH₂)₃-(3-iPr-Ph) H H H H 5-843 H H Me 2 —C≡C—(CH₂)₃-(4-iPr-Ph) H HH H 5-844 H H Me 2 —C≡C—(CH₂)₃-(3-Bu-Ph) H H H H 5-845 H H Me 2—C≡C—(CH₂)₃-(4-Bu-Ph) H H H H 5-846 H H Me 2 —C≡C—(CH₂)₃-(3-CF₃-Ph) H HH H 5-847 H H Me 2 —C≡C—(CH₂)₃-(4-CF₃-Ph) H H H H 5-848 H H Me 2—C≡C—(CH₂)₃-(3-MeO-Ph) H H H H 5-849 H H Me 2 —C≡C—(CH₂)₃-(4-MeO-Ph) H HH H 5-850 H H Me 2 —C≡C—(CH₂)₃-(3-EtO-Ph) H H H H 5-851 H H Me 2—C≡C—(CH₂)₃-(4-EtO-Ph) H H H H 5-852 H H Me 2 —C≡C—(CH₂)₃-(3-PrO-Ph) H HH H 5-853 H H Me 2 —C≡C—(CH₂)₃-(4-PrO-Ph) H H H H 5-854 H H Me 2—C≡C—(CH₂)₃-(3-iPrO-Ph) H H H H 5-855 H H Me 2 —C≡C—(CH₂)₃-(4-iPrO-Ph) HH H H 5-856 H H Me 2 —C≡C—(CH₂)₃-[3-(2-Et-PrO)-Ph] H H H H 5-857 H H Me2 —C≡C—(CH₂)₃-[4-(2-Et-PrO)-Ph] H H H H 5-858 H H Me 2—C≡C—(CH₂)₃-(3-iBuO-Ph) H H H H 5-859 H H Me 2 —C≡C—(CH₂)₃-(4-iBuO-Ph) HH H H 5-860 H H Me 2 —C≡C—(CH₂)₃-(3-MeS-Ph) H H H H 5-861 H H Me 2—C≡C—(CH₂)₃-(4-MeS-Ph) H H H H 5-862 H H Me 2 —C≡C—(CH₂)₃-(3-EtS-Ph) H HH H 5-863 H H Me 2 —C≡C—(CH₂)₃-(4-EtS-Ph) H H H H 5-864 H H Me 2—C≡C—(CH₂)₃-(3-PrS-Ph) H H H H 5-865 H H Me 2 —C≡C—(CH₂)₃-(4-PrS-Ph) H HH H 5-866 H H Me 2 —C≡C—(CH₂)₃-(3-iPrS-Ph) H H H H 5-867 H H Me 2—C≡C—(CH₂)₃-(4-iPrS-Ph) H H H H 5-868 H H Me 2—C≡C—(CH₂)₃-[3-(2-Et-PrS)-Ph] H H H H 5-869 H H Me 2—C≡C—(CH₂)₃-[4-(2-Et-PrS)-Ph] H H H H 5-870 H H Me 2—C≡C—(CH₂)₃-(3-iBuS-Ph) H H H H 5-871 H H Me 2 —C≡C—(CH₂)₃-(4-iBuS-Ph) HH H H 5-872 H H Me 2 —C≡C—(CH₂)₃-(3-cHx-Ph) H H H H 5-873 H H Me 2—C≡C—(CH₂)₃-(4-cHx-Ph) H H H H 5-874 H H Me 2 —C≡C—(CH₂)₃-(3-Ph-Ph) H HH H 5-875 H H Me 2 —C≡C—(CH₂)₃-(4-Ph-Ph) H H H H 5-876 H H Me 2—C≡C—(CH₂)₃-(2,4-diMe-Ph) H H H H 5-877 H H Me 2—C≡C—(CH₂)₃-(3,4-diMe-Ph) H H H H 5-878 H H Me 2—C≡C—(CH₂)₃-(3,5-diMe-Ph) H H H H 5-879 H H Me 2 —C≡C—(CH₂)₃-Np(1) H H HH 5-880 H H Me 2 —C≡C—(CH₂)₃-Np(2) H H H H 5-881 H H Me 2—C≡C—(CH₂)₄-cPn H H H H 5-882 H H Me 2 —C≡C—(CH₂)₄-cHx H H H H 5-883 H HMe 2 —C≡C—(CH₂)₄-cHx Me H H H 5-884 H H Me 2 —C≡C—(CH₂)₄-cHx H Me H H5-885 H H Me 2 —C≡C—(CH₂)₄-cHx F H H H 5-886 H H Me 2 —C≡C—(CH₂)₄-cHx HF H H 5-887 H Me Me 2 —C≡C—(CH₂)₄-cHx H H H H 5-888 CO₂Me H Me 2—C≡C—(CH₂)₄-cHx H H H H 5-889 CO₂Et H Me 2 —C≡C—(CH₂)₄-cHx H H H H 5-890H H Me 2 —C≡C—(CH₂)₄-(3-F-cHx) H H H H 5-891 H H Me 2—C≡C—(CH₂)₄-(4-F-cHx) H H H H 5-892 H H Me 2 —C≡C—(CH₂)₄-(4-Cl-cHx) H HH H 5-893 H H Me 2 —C≡C—(CH₂)₄-(4-Br-cHx) H H H H 5-894 H H Me 2—C≡C—(CH₂)₄-(3-Me-cHx) H H H H 5-895 H H Me 2 —C≡C—(CH₂)₄-(4-Me-cHx) H HH H 5-896 H H Me 2 —C≡C—(CH₂)₄-(3-Et-cHx) H H H H 5-897 H H Me 2—C≡C—(CH₂)₄-(4-Et-cHx) H H H H 5-898 H H Me 2 —C≡C—(CH₂)₄-(3-Pr-cHx) H HH H 5-899 H H Me 2 —C≡C—(CH₂)₄-(4-Pr-cHx) H H H H 5-900 H H Me 2—C≡C—(CH₂)₄-(4-iPr-cHx) H H H H 5-901 H H Me 2 —C≡C—(CH₂)₄-(3-Bu-cHx) HH H H 5-902 H H Me 2 —C≡C—(CH₂)₄-(4-Bu-cHx) H H H H 5-903 H H Me 2—C≡C—(CH₂)₄-(3-CF₃-cHx) H H H H 5-904 H H Me 2 —C≡C—(CH₂)₄-(4-CF₃-cHx) HH H H 5-905 H H Me 2 —C≡C—(CH₂)₄-(3-MeO-cHx) H H H H 5-906 H H Me 2—C≡C—(CH₂)₄-(4-MeO-cHx) H H H H 5-907 H H Me 2 —C≡C—(CH₂)₄-(3-EtO-cHx) HH H H 5-908 H H Me 2 —C≡C—(CH₂)₄-(4-EtO-cHx) H H H H 5-909 H H Me 2—C≡C—(CH₂)₄-(3-PrO-cHx) H H H H 5-910 H H Me 2 —C≡C—(CH₂)₄-(4-PrO-cHx) HH H H 5-911 H H Me 2 —C≡C—(CH₂)₄-(3-iPrO-cHx) H H H H 5-912 H H Me 2—C≡C—(CH₂)₄-(4-iPrO-cHx) H H H H 5-913 H H Me 2—C≡C—(CH₂)₄-[3-(2-Et-PrO)-cHx] H H H H 5-914 H H Me 2—C≡C—(CH₂)₄-[4-(2-Et-PrO)-cHx] H H H H 5-915 H H Me 2—C≡C—(CH₂)₄-(3-iBuO-cHx) H H H H 5-916 H H Me 2 —C≡C—(CH₂)₄-(4-iBuO-cHx)H H H H 5-917 H H Me 2 —C≡C—(CH₂)₄-(3-MeS-cHx) H H H H 5-918 H H Me 2—C≡C—(CH₂)₄-(4-MeS-cHx) H H H H 5-919 H H Me 2 —C≡C—(CH₂)₄-(3-EtS-cHx) HH H H 5-920 H H Me 2 —C≡C—(CH₂)₄-(4-EtS-cHx) H H H H 5-921 H H Me 2—C≡C—(CH₂)₄-(3-PrS-cHx) H H H H 5-922 H H Me 2 —C≡C—(CH₂)₄-(4-PrS-cHx) HH H H 5-923 H H Me 2 —C≡C—(CH₂)₄-(3-iPrS-cHx) H H H H 5-924 H H Me 2—C≡C—(CH₂)₄-(4-iPrS-cHx) H H H H 5-925 H H Me 2—C≡C—(CH₂)₄-[3-(2-Et-PrS)-cHx] H H H H 5-926 H H Me 2—C≡C—(CH₂)₄-[4-(2-Et-PrS)-cHx] H H H H 5-927 H H Me 2—C≡C—(CH₂)₄-(3-iBuS-cHx) H H H H 5-928 H H Me 2 —C≡C—(CH₂)₄-(4-iBuS-cHx)H H H H 5-929 H H Me 2 —C≡C—(CH₂)₄-(3-cHx-cHx) H H H H 5-930 H H Me 2—C≡C—(CH₂)₄-(4-cHx-cHx) H H H H 5-931 H H Me 2 —C≡C—(CH₂)₄-(3-Ph-cHx) HH H H 5-932 H H Me 2 —C≡C—(CH₂)₄-(4-Ph-cHx) H H H H 5-933 H H Me 2—C≡C—(CH₂)₄-(2,4-diMe-cHx) H H H H 5-934 H H Me 2—C≡C—(CH₂)₄-(3,4-diMe-cHx) H H H H 5-935 H H Me 2—C≡C—(CH₂)₄-(3,5-diMe-cHx) H H H H 5-936 H H Me 2 —C≡C—(CH₂)₄-Ph H H H H5-937 H H Me 2 —C≡C—(CH₂)₄-Ph Me H H H 5-938 H H Me 2 —C≡C—(CH₂)₄-Ph HMe H H 5-939 H H Me 2 —C≡C—(CH₂)₄-Ph F H H H 5-940 H H Me 2—C≡C—(CH₂)₄-Ph H F H H 5-941 H Me Me 2 —C≡C—(CH₂)₄-Ph H H H H 5-942CO₂Me H Me 2 —C≡C—(CH₂)₄-Ph H H H H 5-943 CO₂Et H Me 2 —C≡C—(CH₂)₄-Ph HH H H 5-944 H H Me 2 —C≡C—(CH₂)₄-(3-F-Ph) H H H H 5-945 H H Me 2—C≡C—(CH₂)₄-(4-F-Ph) H H H H 5-946 H H Me 2 —C≡C—(CH₂)₄-(4-Cl-Ph) H H HH 5-947 H H Me 2 —C≡C—(CH₂)₄-(4-Br-Ph) H H H H 5-948 H H Me 2—C≡C—(CH₂)₄-(3-Me-Ph) H H H H 5-949 H H Me 2 —C≡C—(CH₂)₄-(4-Me-Ph) H H HH 5-950 H H Me 2 —C≡C—(CH₂)₄-(3-Et-Ph) H H H H 5-951 H H Me 2—C≡C—(CH₂)₄-(4-Et-Ph) H H H H 5-952 H H Me 2 —C≡C—(CH₂)₄-(3-Pr-Ph) H H HH 5-953 H H Me 2 —C≡C—(CH₂)₄-(4-Pr-Ph) H H H H 5-954 H H Me 2—C≡C—(CH₂)₄-(3-iPr-Ph) H H H H 5-955 H H Me 2 —C≡C—(CH₂)₄-(4-iPr-Ph) H HH H 5-956 H H Me 2 —C≡C—(CH₂)₄-(3-Bu-Ph) H H H H 5-957 H H Me 2—C≡C—(CH₂)₄-(4-Bu-Ph) H H H H 5-958 H H Me 2 —C≡C—(CH₂)₄-(3-CF₃-Ph) H HH H 5-959 H H Me 2 —C≡C—(CH₂)₄-(4-CF₃-Ph) H H H H 5-960 H H Me 2—C≡C—(CH₂)₄-(3-MeO-Ph) H H H H 5-961 H H Me 2 —C≡C—(CH₂)₄-(4-MeO-Ph) H HH H 5-962 H H Me 2 —C≡C—(CH₂)₄-(3-EtO-Ph) H H H H 5-963 H H Me 2—C≡C—(CH₂)₄-(4-EtO-Ph) H H H H 5-964 H H Me 2 —C≡C—(CH₂)₄-(3-PrO-Ph) H HH H 5-965 H H Me 2 —C≡C—(CH₂)₄-(4-PrO-Ph) H H H H 5-966 H H Me 2—C≡C—(CH₂)₄-(3-iPrO-Ph) H H H H 5-967 H H Me 2 —C≡C—(CH₂)₄-(4-iPrO-Ph) HH H H 5-968 H H Me 2 —C≡C—(CH₂)₄-[3-(2-Et-PrO)-Ph] H H H H 5-969 H H Me2 —C≡C—(CH₂)₄-[4-(2-Et-PrO)-Ph] H H H H 5-970 H H Me 2—C≡C—(CH₂)₄-(3-iBuO-Ph) H H H H 5-971 H H Me 2 —C≡C—(CH₂)₄-(4-iBuO-Ph) HH H H 5-972 H H Me 2 —C≡C—(CH₂)₄-(3-MeS-Ph) H H H H 5-973 H H Me 2—C≡C—(CH₂)₄-(4-MeS-Ph) H H H H 5-974 H H Me 2 —C≡C—(CH₂)₄-(3-EtS-Ph) H HH H 5-975 H H Me 2 —C≡C—(CH₂)₄-(4-EtS-Ph) H H H H 5-976 H H Me 2—C≡C—(CH₂)₄-(3-PrS-Ph) H H H H 5-977 H H Me 2 —C≡C—(CH₂)₄-(4-PrS-Ph) H HH H 5-978 H H Me 2 —C≡C—(CH₂)₄-(3-iPrS-Ph) H H H H 5-979 H H Me 2—C≡C—(CH₂)₄-(4-iPrS-Ph) H H H H 5-980 H H Me 2—C≡C—(CH₂)₄-[3-(2-Et-PrS)-Ph] H H H H 5-981 H H Me 2—C≡C—(CH₂)₄-[4-(2-Et-PrS)-Ph] H H H H 5-982 H H Me 2—C≡C—(CH₂)₄-(3-iBuS-Ph) H H H H 5-983 H H Me 2 —C≡C—(CH₂)₄-(4-iBuS-Ph) HH H H 5-984 H H Me 2 —C≡C—(CH₂)₄-(3-cHx-Ph) H H H H 5-985 H H Me 2—C≡C—(CH₂)₄-(4-cHx-Ph) H H H H 5-986 H H Me 2 —C≡C—(CH₂)₄-(3-Ph-Ph) H HH H 5-987 H H Me 2 —C≡C—(CH₂)₄-(4-Ph-Ph) H H H H 5-988 H H Me 2—C≡C—(CH₂)₄-(2,4-diMe-Ph) H H H H 5-989 H H Me 2—C≡C—(CH₂)₄-(3,4-diMe-Ph) H H H H 5-990 H H Me 2—C≡C—(CH₂)₄-(3,5-diMe-Ph) H H H H 5-991 H H Me 2 —C≡C—(CH₂)₄-Np(1) H H HH 5-992 H H Me 2 —C≡C—(CH₂)₄-Np(2) H H H H 5-993 H H Me 2—C≡C—(CH₂)₅-cHx H H H H 5-994 H Me Me 2 —C≡C—(CH₂)₅-cHx H H H H 5-995CO₂Me H Me 2 —C≡C—(CH₂)₅-cHx H H H H 5-996 CO₂Et H Me 2 —C≡C—(CH₂)₅-cHxH H H H 5-997 H H Me 2 —C≡C—(CH₂)₅-(4-F-cHx) H H H H 5-998 H H Me 2—C≡C—(CH₂)₅-(4-Me-cHx) H H H H 5-999 H H Me 2 —C≡C—(CH₂)₅-(4-Et-cHx) H HH H 5-1000 H H Me 2 —C≡C—(CH₂)₅-(4-CF₃-cHx) H H H H 5-1001 H H Me 2—C≡C—(CH₂)₅-(4-MeO-cHx) H H H H 5-1002 H H Me 2 —C≡C—(CH₂)₅-(4-EtO-cHx)H H H H 5-1003 H H Me 2 —C≡C—(CH₂)₅-(4-MeS-cHx) H H H H 5-1004 H H Me 2—C≡C—(CH₂)₅-(4-cHx-cHx) H H H H 5-1005 H H Me 2 —C≡C—(CH₂)₅-(4-Ph-cHx) HH H H 5-1006 H H Me 2 —C≡C—(CH₂)₅-Ph H H H H 5-1007 H Me Me 2—C≡C—(CH₂)₅-Ph H H H H 5-1008 CO₂Me H Me 2 —C≡C—(CH₂)₅-Ph H H H H 5-1009CO₂Et H Me 2 —C≡C—(CH₂)₅-Ph H H H H 5-1010 H H Me 2 —C≡C—(CH₂)₅-(4-F-Ph)H H H H 5-1011 H H Me 2 —C≡C—(CH₂)₅-(4-Me-Ph) H H H H 5-1012 H H Me 2—C≡C—(CH₂)₅-(4-Et-Ph) H H H H 5-1013 H H Me 2 —C≡C—(CH₂)₅-(4-CF₃-Ph) H HH H 5-1014 H H Me 2 —C≡C—(CH₂)₅-(4-MeO-Ph) H H H H 5-1015 H H Me 2—C≡C—(CH₂)₅-(4-EtO-Ph) H H H H 5-1016 H H Me 2 —C≡C—(CH₂)₅-(4-MeS-Ph) HH H H 5-1017 H H Me 2 —C≡C—(CH₂)₅-(4-cHx-Ph) H H H H 5-1018 H H Me 2—C≡C—(CH₂)₅-(4-Ph-Ph) H H H H 5-1019 H H Me 2 —C≡C—(CH₂)₆-cHx H H H H5-1020 H Me Me 2 —C≡C—(CH₂)₆-cHx H H H H 5-1021 CO₂Me H Me 2—C≡C—(CH₂)₆-cHx H H H H 5-1022 CO₂Et H Me 2 —C≡C—(CH₂)₆-cHx H H H H5-1023 H H Me 2 —C≡C—(CH₂)₆-(4-F-cHx) H H H H 5-1024 H H Me 2—C≡C—(CH₂)₆-(4-Me-cHx) H H H H 5-1025 H H Me 2 —C≡C—(CH₂)₆-(4-Et-cHx) HH H H 5-1026 H H Me 2 —C≡C—(CH₂)₆-(4-CF₃-cHx) H H H H 5-1027 H H Me 2—C≡C—(CH₂)₆-(4-MeO-cHx) H H H H 5-1028 H H Me 2 —C≡C—(CH₂)₆-(4-EtO-cHx)H H H H 5-1029 H H Me 2 —C≡C—(CH₂)₆-(4-MeS-cHx) H H H H 5-1030 H H Me 2—C≡C—(CH₂)₆-(4-cHx-cHx) H H H H 5-1031 H H Me 2 —C≡C—(CH₂)₆-(4-Ph-cHx) HH H H 5-1032 H H Me 2 —C≡C—(CH₂)₆-Ph H H H H 5-1033 H Me Me 2—C≡C—(CH₂)₆-Ph H H H H 5-1034 CO₂Me H Me 2 —C≡C—(CH₂)₆-Ph H H H H 5-1035CO₂Et H Me 2 —C≡C—(CH₂)₆-Ph H H H H 5-1036 H H Me 2 —C≡C—(CH₂)₆-(4-F-Ph)H H H H 5-1037 H H Me 2 —C≡C—(CH₂)₆-(4-Me-Ph) H H H H 5-1038 H H Me 2—C≡C—(CH₂)₆-(4-Et-Ph) H H H H 5-1039 H H Me 2 —C≡C—(CH₂)₆-(4-CF₃-Ph) H HH H 5-1040 H H Me 2 —C≡C—(CH₂)₆-(4-MeO-Ph) H H H H 5-1041 H H Me 2—C≡C—(CH₂)₆-(4-EtO-Ph) H H H H 5-1042 H H Me 2 —C≡C—(CH₂)₆-(4-MeS-Ph) HH H H 5-1043 H H Me 2 —C≡C—(CH₂)₆-(4-cHx-Ph) H H H H 5-1044 H H Me 2—C≡C—(CH₂)₆-(4-Ph-Ph) H H H H 5-1045 H H Me 2 —C≡C—CH₂—O-cHx H H H H5-1046 H Me Me 2 —C≡C—CH₂—O-cHx H H H H 5-1047 CO₂Me H Me 2—C≡C—CH₂—O-cHx H H H H 5-1048 CO₂Et H Me 2 —C≡C—CH₂—O-cHx H H H H 5-1049H H Me 2 —C≡C—CH₂—O-(4-F-cHx) H H H H 5-1050 H H Me 2—C≡C—CH₂—O-(4-Me-cHx) H H H H 5-1051 H H Me 2 —C≡C—CH₂—O-(4-Et-cHx) H HH H 5-1052 H H Me 2 —C≡C—CH₂—O-(4-CF₃-cHx) H H H H 5-1053 H H Me 2—C≡C—CH₂—O-(4-MeO-cHx) H H H H 5-1054 H H Me 2 —C≡C—CH₂—O-(4-EtO-cHx) HH H H 5-1055 H H Me 2 —C≡C—CH₂—O-(4-MeS-cHx) H H H H 5-1056 H H Me 2—C≡C—CH₂—O-(4-cHx-cHx) H H H H 5-1057 H H Me 2 —C≡C—CH₂—O-(4-Ph-cHx) H HH H 5-1058 H H Me 2 —C≡C—CH₂—O-Ph H H H H 5-1059 H Me Me 2 —C≡C—CH₂—O-PhH H H H 5-1060 CO₂Me H Me 2 —C≡C—CH₂—O-Ph H H H H 5-1061 CO₂Et H Me 2—C≡C—CH₂—O-Ph H H H H 5-1062 H H Me 2 —C≡C—CH₂—O-(4-F-Ph) H H H H 5-1063H H Me 2 —C≡C—CH₂—O-(4-Me-Ph) H H H H 5-1064 H H Me 2—C≡C—CH₂—O-(4-Et-Ph) H H H H 5-1065 H H Me 2 —C≡C—CH₂—O-(4-CF₃-Ph) H H HH 5-1066 H H Me 2 —C≡C—CH₂—O-(4-MeO-Ph) H H H H 5-1067 H H Me 2—C≡C—CH₂—O-(4-EtO-Ph) H H H H 5-1068 H H Me 2 —C≡C—CH₂—O-(4-MeS-Ph) H HH H 5-1069 H H Me 2 —C≡C—CH₂—O-(4-cHx-Ph) H H H H 5-1070 H H Me 2—C≡C—CH₂—O-(4-Ph-Ph) H H H H 5-1071 H H Me 2 —C≡C—(CH₂)₂O-cPn H H H H5-1072 H H Me 2 —C≡C—(CH₂)₂O-cHx H H H H 5-1073 H H Me 2—C≡C—(CH₂)₂O-cHx Me H H H 5-1074 H H Me 2 —C≡C—(CH₂)₂O-cHx H Me H H5-1075 H H Me 2 —C≡C—(CH₂)₂O-cHx F H H H 5-1076 H H Me 2—C≡C—(CH₂)₂O-cHx H F H H 5-1077 H Me Me 2 —C≡C—(CH₂)₂O-cHx H H H H5-1078 CO₂Me H Me 2 —C≡C—(CH₂)₂O-cHx H H H H 5-1079 CO₂Et H Me 2—C≡C—(CH₂)₂O-cHx H H H H 5-1080 H H Me 2 —C≡C—(CH₂)₂O-(3-F-cHx) H H H H5-1081 H H Me 2 —C≡C—(CH₂)₂O-(4-F-cHx) H H H H 5-1082 H H Me 2—C≡C—(CH₂)₂O-(4-Cl-cHx) H H H H 5-1083 H H Me 2 —C≡C—(CH₂)₂O-(4-Br-cHx)H H H H 5-1084 H H Me 2 —C≡C—(CH₂)₂O-(3-Me-cHx) H H H H 5-1085 H H Me 2—C≡C—(CH₂)₂O-(4-Me-cHx) H H H H 5-1086 H H Me 2 —C≡C—(CH₂)₂O-(3-Et-cHx)H H H H 5-1087 H H Me 2 —C≡C—(CH₂)₂O-(4-Et-cHx) H H H H 5-1088 H H Me 2—C≡C—(CH₂)₂O-(3-Pr-cHx) H H H H 5-1089 H H Me 2 —C≡C—(CH₂)₂O-(4-Pr-cHx)H H H H 5-1090 H H Me 2 —C≡C—(CH₂)₂O-(4-iPr-cHx) H H H H 5-1091 H H Me 2—C≡C—(CH₂)₂O-(3-Bu-cHx) H H H H 5-1092 H H Me 2 —C≡C—(CH₂)₂O-(4-Bu-cHx)H H H H 5-1093 H H Me 2 —C≡C—(CH₂)₂O-(3-CF₃-cHx) H H H H 5-1094 H H Me 2—C≡C—(CH₂)₂O-(4-CF₃-cHx) H H H H 5-1095 H H Me 2—C≡C—(CH₂)₂O-(3-MeO-cHx) H H H H 5-1096 H H Me 2—C≡C—(CH₂)₂O-(4-MeO-cHx) H H H H 5-1097 H H Me 2—C≡C—(CH₂)₂O-(3-EtO-cHx) H H H H 5-1098 H H Me 2—C≡C—(CH₂)₂O-(4-EtO-cHx) H H H H 5-1099 H H Me 2—C≡C—(CH₂)₂O-(3-PrO-cHx) H H H H 5-1100 H H Me 2—C≡C—(CH₂)₂O-(4-PrO-cHx) H H H H 5-1101 H H Me 2—C≡C—(CH₂)₂O-(3-iPrO-cHx) H H H H 5-1102 H H Me 2—C≡C—(CH₂)₂O-(4-iPrO-cHx) H H H H 5-1103 H H Me 2—C≡C—(CH₂)₂O-[3-(2-Et-PrO)-cHx] H H H H 5-1104 H H Me 2—C≡C—(CH₂)₂O-[4-(2-Et-PrO)-cHx] H H H H 5-1105 H H Me 2—C≡C—(CH₂)₂O-(3-iBuO-cHx) H H H H 5-1106 H H Me 2—C≡C—(CH₂)₂O-(4-iBuO-cHx) H H H H 5-1107 H H Me 2—C≡C—(CH₂)₂O-(3-MeS-cHx) H H H H 5-1108 H H Me 2—C≡C—(CH₂)₂O-(4-MeS-cHx) H H H H 5-1109 H H Me 2—C≡C—(CH₂)₂O-(3-EtS-cHx) H H H H 5-1110 H H Me 2—C≡C—(CH₂)₂O-(4-EtS-cHx) H H H H 5-1111 H H Me 2—C≡C—(CH₂)₂O-(3-PrS-cHx) H H H H 5-1112 H H Me 2—C≡C—(CH₂)₂O-(4-PrS-cHx) H H H H 5-1113 H H Me 2—C≡C—(CH₂)₂O-(3-iPrS-cHx) H H H H 5-1114 H H Me 2—C≡C—(CH₂)₂O-(4-iPrS-cHx) H H H H 5-1115 H H Me 2—C≡C—(CH₂)₂O-[3-(2-Et-PrS)-cHx] H H H H 5-1116 H H Me 2—C≡C—(CH₂)₂O-[4-(2-Et-PrS)-cHx] H H H H 5-1117 H H Me 2—C≡C—(CH₂)₂O-(3-iBuS-cHx) H H H H 5-1118 H H Me 2—C≡C—(CH₂)₂O-(4-iBuS-cHx) H H H H 5-1119 H H Me 2—C≡C—(CH₂)₂O-(3-cHx-cHx) H H H H 5-1120 H H Me 2—C≡C—(CH₂)₂O-(4-cHx-cHx) H H H H 5-1121 H H Me 2 —C≡C—(CH₂)₂O-(3-Ph-cHx)H H H H 5-1122 H H Me 2 —C≡C—(CH₂)₂O-(4-Ph-cHx) H H H H 5-1123 H H Me 2—C≡C—(CH₂)₂O-(2,4-diMe-cHx) H H H H 5-1124 H H Me 2—C≡C—(CH₂)₂O-(3,4-diMe-cHx) H H H H 5-1125 H H Me 2—C≡C—(CH₂)₂O-(3,5-diMe-cHx) H H H H 5-1126 H H Me 2 —C≡C—(CH₂)₂O-Ph H HH H 5-1127 H H Me 2 —C≡C—(CH₂)₂O-Ph Me H H H 5-1128 H H Me 2—C≡C—(CH₂)₂O-Ph H Me H H 5-1129 H H Me 2 —C≡C—(CH₂)₂O-Ph F H H H 5-1130H H Me 2 —C≡C—(CH₂)₂O-Ph H F H H 5-1131 H Me Me 2 —C≡C—(CH₂)₂O-Ph H H HH 5-1132 CO₂Me H Me 2 —C≡C—(CH₂)₂O-Ph H H H H 5-1133 CO₂Et H Me 2—C≡C—(CH₂)₂O-Ph H H H H 5-1134 H H Me 2 —C≡C—(CH₂)₂O-(3-F-Ph) H H H H5-1135 H H Me 2 —C≡C—(CH₂)₂O-(4-F-Ph) H H H H 5-1136 H H Me 2—C≡C—(CH₂)₂O-(4-Cl-Ph) H H H H 5-1137 H H Me 2 —C≡C—(CH₂)₂O-(4-Br-Ph) HH H H 5-1138 H H Me 2 —C≡C—(CH₂)₂O-(3-Me-Ph) H H H H 5-1139 H H Me 2—C≡C—(CH₂)₂O-(4-Me-Ph) H H H H 5-1140 H H Me 2 —C≡C—(CH₂)₂O-(3-Et-Ph) HH H H 5-1141 H H Me 2 —C≡C—(CH₂)₂O-(4-Et-Ph) H H H H 5-1142 H H Me 2—C≡C—(CH₂)₂O-(3-Pr-Ph) H H H H 5-1143 H H Me 2 —C≡C—(CH₂)₂O-(4-Pr-Ph) HH H H 5-1144 H H Me 2 —C≡C—(CH₂)₂O-(3-iPr-Ph) H H H H 5-1145 H H Me 2—C≡C—(CH₂)₂O-(4-iPr-Ph) H H H H 5-1146 H H Me 2 —C≡C—(CH₂)₂O-(3-Bu-Ph) HH H H 5-1147 H H Me 2 —C≡C—(CH₂)₂O-(4-Bu-Ph) H H H H 5-1148 H H Me 2—C≡C—(CH₂)₂O-(3-CF₃-Ph) H H H H 5-1149 H H Me 2 —C≡C—(CH₂)₂O-(4-CF₃-Ph)H H H H 5-1150 H H Me 2 —C≡C—(CH₂)₂O-(3-MeO-Ph) H H H H 5-1151 H H Me 2—C≡C—(CH₂)₂O-(4-MeO-Ph) H H H H 5-1152 H H Me 2 —C≡C—(CH₂)₂O-(3-EtO-Ph)H H H H 5-1153 H H Me 2 —C≡C—(CH₂)₂O-(4-EtO-Ph) H H H H 5-1154 H H Me 2—C≡C—(CH₂)₂O-(3-PrO-Ph) H H H H 5-1155 H H Me 2 —C≡C—(CH₂)₂O-(4-PrO-Ph)H H H H 5-1156 H H Me 2 —C≡C—(CH₂)₂O-(3-iPrO-Ph) H H H H 5-1157 H H Me 2—C≡C—(CH₂)₂O-(4-iPrO-Ph) H H H H 5-1158 H H Me 2—C≡C—(CH₂)₂O-[3-(2-Et-PrO)-Ph] H H H H 5-1159 H H Me 2—C≡C—(CH₂)₂O-[4-(2-Et-PrO)-Ph] H H H H 5-1160 H H Me 2—C≡C—(CH₂)₂O-(3-iBuO-Ph) H H H H 5-1161 H H Me 2—C≡C—(CH₂)₂O-(4-iBuO-Ph) H H H H 5-1162 H H Me 2 —C≡C—(CH₂)₂O-(3-MeS-Ph)H H H H 5-1163 H H Me 2 —C≡C—(CH₂)₂O-(4-MeS-Ph) H H H H 5-1164 H H Me 2—C≡C—(CH₂)₂O-(3-EtS-Ph) H H H H 5-1165 H H Me 2 —C≡C—(CH₂)₂O-(4-EtS-Ph)H H H H 5-1166 H H Me 2 —C≡C—(CH₂)₂O-(3-PrS-Ph) H H H H 5-1167 H H Me 2—C≡C—(CH₂)₂O-(4-PrS-Ph) H H H H 5-1168 H H Me 2 —C≡C—(CH₂)₂O-(3-iPrS-Ph)H H H H 5-1169 H H Me 2 —C≡C—(CH₂)₂O-(4-iPrS-Ph) H H H H 5-1170 H H Me 2—C≡C—(CH₂)₂O-[3-(2-Et-PrS)-Ph] H H H H 5-1171 H H Me 2—C≡C—(CH₂)₂O-[4-(2-Et-PrS)-Ph] H H H H 5-1172 H H Me 2—C≡C—(CH₂)₂O-(3-iBuS-Ph) H H H H 5-1173 H H Me 2—C≡C—(CH₂)₂O-(4-iBuS-Ph) H H H H 5-1174 H H Me 2 —C≡C—(CH₂)₂O-(3-cHx-Ph)H H H H 5-1175 H H Me 2 —C≡C—(CH₂)₂O-(4-cHx-Ph) H H H H 5-1176 H H Me 2—C≡C—(CH₂)₂O-(3-Ph-Ph) H H H H 5-1177 H H Me 2 —C≡C—(CH₂)₂O-(4-Ph-Ph) HH H H 5-1178 H H Me 2 —C≡C—(CH₂)₂O-(2,4-diMe-Ph) H H H H 5-1179 H H Me 2—C═C—(CH₂)₂O-(3,4-diMe-Ph) H H H H 5-1180 H H Me 2—C≡C—(CH₂)₂O-(3,5-diMe-Ph) H H H H 5-1181 H H Me 2 —C≡C—(CH₂)₃O-cHx H HH H 5-1182 H H Me 2 —C≡C—(CH₂)₃O-Ph H H H H 5-1183 H H Me 2—C≡C—(CH₂)₄O-cHx H H H H 5-1184 H H Me 2 —C≡C—(CH₂)₄O-Ph H H H H 5-1185H H Me 2 —C≡C—CH₂—OCH₂-cHx H H H H 5-1186 H Me Me 2 —C≡C—CH₂—OCH₂-cHx HH H H 5-1187 CO₂Me H Me 2 —C≡C—CH₂—OCH₂-cHx H H H H 5-1188 CO₂Et H Me 2—C≡C—CH₂—OCH₂-cHx H H H H 5-1189 H H Me 2 —C≡C—CH₂—OCH₂-(4-F-cHx) H H HH 5-1190 H H Me 2 —C≡C—CH₂—OCH₂-(4-Me-cHx) H H H H 5-1191 H H Me 2—C≡C—CH₂—OCH₂-(4-Et-cHx) H H H H 5-1192 H H Me 2—C≡C—CH₂—OCH₂-(4-CF₃-cHx) H H H H 5-1193 H H Me 2—C≡C—CH₂—OCH₂-(4-MeO-cHx) H H H H 5-1194 H H Me 2—C≡C—CH₂—OCH₂-(4-EtO-cHx) H H H H 5-1195 H H Me 2—C≡C—CH₂—OCH₂-(4-MeS-cHx) H H H H 5-1196 H H Me 2—C≡C—CH₂—OCH₂-(4-cHx-cHx) H H H H 5-1197 H H Me 2—C≡C—CH₂—OCH₂-(4-Ph-cHx) H H H H 5-1198 H H Me 2 —C≡C—CH₂—OCH₂-Ph H H HH 5-1199 H Me Me 2 —C≡C—CH₂—OCH₂-Ph H H H H 5-1200 CO₂Me H Me 2—C≡C—CH₂—OCH₂-Ph H H H H 5-1201 —CO₂Et H Me 2 —C≡C—CH₂—OCH₂-Ph H H H H5-1202 H H Me 2 —C≡C—CH₂—OCH₂-(4-F-Ph) H H H H 5-1203 H H Me 2—C≡C—CH₂—OCH₂-(4-Me-Ph) H H H H 5-1204 H H Me 2 —C≡C—CH₂—OCH₂-(4-Et-Ph)H H H H 5-1205 H H Me 2 —C≡C—CH₂—OCH₂-(4-CF₃-Ph) H H H H 5-1206 H H Me 2—C≡C—CH₂—OCH₂-(4-MeO-Ph) H H H H 5-1207 H H Me 2—C≡C—CH₂—OCH₂-(4-EtO-Ph) H H H H 5-1208 H H Me 2—C≡C—CH₂—OCH₂-(4-MeS-Ph) H H H H 5-1209 H H Me 2—C≡C—CH₂—OCH₂-(4-cHx-Ph) H H H H 5-1210 H H Me 2 —C≡C—CH₂—OCH₂-(4-Ph-Ph)H H H H 5-1211 H H Me 2 —C≡C—(CH₂)₂—OCH₂-cPn H H H H 5-1212 H H Me 2—C≡C—(CH₂)₂—OCH₂-cHx H H H H 5-1213 H H Me 2 —C≡C—(CH₂)₂—OCH₂-cHx Me H HH 5-1214 H H Me 2 —C≡C—(CH₂)₂—OCH₂-cHx H Me H H 5-1215 H H Me 2—C≡C—(CH₂)₂—OCH₂-cHx F H H H 5-1216 H H Me 2 —C≡C—(CH₂)₂—OCH₂-cHx H F HH 5-1217 H Me Me 2 —C≡C—(CH₂)₂—OCH₂—CH₂-cHx H H H H 5-1218 CO₂Me H Me 2—C≡C—(CH₂)₂—OCH₂-cHx H H H H 5-1219 CO₂Et H Me 2 —C≡C—(CH₂)₂—OCH₂-cHx HH H H 5-1220 H H Me 2 —C≡C—(CH₂)₂—OCH₂-(3-F-cHx) H H H H 5-1221 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-F-cHx) H H H H 5-1222 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Cl-cHx) H H H H 5-1223 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Br-cHx) H H H H 5-1224 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-Me-cHx) H H H H 5-1225 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Me-cHx) H H H H 5-1226 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-Et-cHx) H H H H 5-1227 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Et-cHx) H H H H 5-1228 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-Pr-cHx) H H H H 5-1229 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Pr-cHx) H H H H 5-1230 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-iPr-cHx) H H H H 5-1231 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-Bu-cHx) H H H H 5-1232 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Bu-cHx) H H H H 5-1233 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-CF₃-cHx) H H H H 5-1234 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-CF₃-cHx) H H H H 5-1235 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-MeO-cHx) H H H H 5-1236 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-MeO-cHx) H H H H 5-1237 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-EtO-cHx) H H H H 5-1238 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-EtO-cHx) H H H H 5-1239 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-PrO-cHx) H H H H 5-1240 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-PrO-cHx) H H H H 5-1241 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-iPrO-cHx) H H H H 5-1242 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-iPrO-cHx) H H H H 5-1243 H H Me 2—C≡C—(CH₂)₂—OCH₂-[3-(2-Et-PrO)cHx] H H H H 5-1244 H H Me 2—C≡C—(CH₂)₂—OCH₂-[4-(2-Et-PrO)cHx] H H H H 5-1245 H H Me 2—C═C—(CH₂)₂—OCH₂-(3-iBuO-cHx) H H H H 5-1246 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-iBuO-cHx) H H H H 5-1247 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-MeS-cHx) H H H H 5-1248 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-MeS-cHx) H H H H 5-1249 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-EtS-cHx) H H H H 5-1250 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-EtS-cHx) H H H H 5-1251 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-PrS-cHx) H H H H 5-1252 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-PrS-cHx) H H H H 5-1253 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-iPrS-cHx) H H H H 5-1254 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-iPrS-cHx) H H H H 5-1255 H H Me 2—C≡C—(CH₂)₂—OCH₂-[3-(2-Et-PrS)cHx] H H H H 5-1256 H H Me 2—C≡C—(CH₂)₂—OCH₂-[4-(2-Et-PrS)cHx] H H H H 5-1257 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-iBuS-cHx) H H H H 5-1258 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-iBuS-cHx) H H H H 5-1259 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-cHx-cHx) H H H H 5-1260 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-cHx-cHx) H H H H 5-1261 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-Ph-cHx) H H H H 5-1262 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Ph-cHx) H H H H 5-1263 H H Me 2—C≡C—(CH₂)₂—OCH₂-(2,4-diMe-cHx) H H H H 5-1264 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3,4-diMe-cHx) H H H H 5-1265 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3,5-diMe-cHx) H H H H 5-1266 H H Me 2—C≡C—(CH₂)₂—OCH₂-Ph H H H H 5-1267 H H Me 2 —C≡C—(CH₂)₂—OCH₂-Ph Me H H H5-1268 H H Me 2 —C≡C—(CH₂)₂—OCH₂-Ph H Me H H 5-1269 H H Me 2—C≡C—(CH₂)₂—OCH₂-Ph F H H H 5-1270 H H Me 2 —C≡C—(CH₂)₂—OCH₂-Ph H F H H5-1271 H Me Me 2 —C≡C—(CH₂)₂—OCH₂—CH₂-Ph H H H H 5-1272 CO₂Me H Me 2—C≡C—(CH₂)₂—OCH₂-Ph H H H H 5-1273 CO₂Et H Me 2 —C≡C—(CH₂)₂—OCH₂-Ph H HH H 5-1274 H H Me 2 —C≡C—(CH₂)₂—OCH₂-(3-F-Ph) H H H H 5-1275 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-F-Ph) H H H H 5-1276 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Cl-Ph) H H H H 5-1277 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Br-Ph) H H H H 5-1278 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-Me-Ph) H H H H 5-1279 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Me-Ph) H H H H 5-1280 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-Et-Ph) H H H H 5-1281 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Et-Ph) H H H H 5-1282 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-Pr-Ph) H H H H 5-1283 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Pr-Ph) H H H H 5-1284 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-iPr-Ph) H H H H 5-1285 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-iPr-Ph) H H H H 5-1286 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-Bu-Ph) H H H H 5-1287 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Bu-Ph) H H H H 5-1288 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-CF₃-Ph) H H H H 5-1289 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-CF₃-Ph) H H H H 5-1290 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-MeO-Ph) H H H H 5-1291 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-MeO-Ph) H H H H 5-1292 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-EtO-Ph) H H H H 5-1293 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-EtO-Ph) H H H H 5-1294 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-PrO-Ph) H H H H 5-1295 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-PrO-Ph) H H H H 5-1296 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-iPrO-Ph) H H H H 5-1297 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-iPrO-Ph) H H H H 5-1298 H H Me 2—C≡C—(CH₂)₂—OCH₂-[3-(2-Et-PrO)Ph] H H H H 5-1299 H H Me 2—C≡C—(CH₂)₂—OCH₂-[4-(2-Et-PrO)Ph] H H H H 5-1300 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-iBuO-Ph) H H H H 5-1301 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-iBuO-Ph) H H H H 5-1302 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-MeS-Ph) H H H H 5-1303 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-MeS-Ph) H H H H 5-1304 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-EtS-Ph) H H H H 5-1305 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-EtS-Ph) H H H H 5-1306 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-PrS-Ph) H H H H 5-1307 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-PrS-Ph) H H H H 5-1308 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-iPrS-Ph) H H H H 5-1309 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-iPrS-Ph) H H H H 5-1310 H H Me 2—C≡C—(CH₂)₂—OCH₂-[3-(2-Et-PrS)Ph] H H H H 5-1311 H H Me 2—C≡C—(CH₂)₂—OCH₂-[4-(2-Et-PrS)Ph] H H H H 5-1312 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-iBuS-Ph) H H H H 5-1313 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-iBuS-Ph) H H H H 5-1314 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-cHx-Ph) H H H H 5-1315 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-cHx-Ph) H H H H 5-1316 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3-Ph-Ph) H H H H 5-1317 H H Me 2—C≡C—(CH₂)₂—OCH₂-(4-Ph-Ph) H H H H 5-1318 H H Me 2—C≡C—(CH₂)₂—OCH₂-(2,4-diMe-Ph) H H H H 5-1319 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3,4-diMe-Ph) H H H H 5-1320 H H Me 2—C≡C—(CH₂)₂—OCH₂-(3,5-diMe-Ph) H H H H 5-1321 H H Me 2—C≡C—(CH₂)₃—OCH₂-cHx H H H H 5-1322 H H Me 2 —C≡C—(CH₂)₃—OCH₂-Ph H H H H5-1323 H H Me 2 —C≡C—(CH₂)₄—OCH₂-cHx H H H H 5-1324 H H Me 2—C≡C—(CH₂)₄—OCH₂-Ph H H H H 5-1325 H H Me 2 —CO—CH₂-(4-cHx-Ph) H H H H5-1326 H H Me 2 —CO—CH₂-(4-Ph-Ph) H H H H 5-1327 H H Me 2 —CO—(CH₂)₂-cHxH H H H 5-1328 H H Me 2 —CO—(CH₂)₂-Ph H H H H 5-1329 H H Me 2—CO—(CH₂)₃-cHx H H H H 5-1330 H H Me 2 —CO—(CH₂)₃-Ph H H H H 5-1331 H HMe 2 —CO—(CH₂)₄-cHx H H H H 5-1332 H Me Me 2 —CO—(CH₂)₄-cHx H H H H5-1333 CO₂Me H Me 2 —CO—(CH₂)₄-cHx H H H H 5-1334 CO₂Et H Me 2—CO—(CH₂)₄-cHx H H H H 5-1335 H H Me 2 —CO—(CH₂)₄-(4-F-cHx) H H H H5-1336 H H Me 2 —CO—(CH₂)₄-(4-Me-cHx) H H H H 5-1337 H H Me 2—CO—(CH₂)₄-(4-Et-cHx) H H H H 5-1338 H H Me 2 —CO—(CH₂)₄-(4-CF₃-cHx) H HH H 5-1339 H H Me 2 —CO—(CH₂)₄-(4-MeO-cHx) H H H H 5-1340 H H Me 2—CO—(CH₂)₄-(4-EtO-cHx) H H H H 5-1341 H H Me 2 —CO—(CH₂)₄-(4-MeS-cHx) HH H H 5-1342 H H Me 2 —CO—(CH₂)₄-(4-cHx-cHx) H H H H 5-1343 H H Me 2—CO—(CH₂)₄-(4-Ph-cHx) H H H H 5-1344 H H Me 2 —CO—(CH₂)₄-Ph H H H H5-1345 H Me Me 2 —CO—(CH₂)₄-Ph H H H H 5-1346 CO₂Me H Me 2 —CO—(CH₂)₄-PhH H H H 5-1347 CO₂Et H Me 2 —CO—(CH₂)₄-Ph H H H H 5-1348 H H Me 2—CO—(CH₂)₄-(4-F-Ph) H H H H 5-1349 H H Me 2 —CO—(CH₂)₄-(4-Me-Ph) H H H H5-1350 H H Me 2 —CO—(CH₂)₄-(4-Et-Ph) H H H H 5-1351 H H Me 2—CO—(CH₂)₄-(4-CF₃-Ph) H H H H 5-1352 H H Me 2 —CO—(CH₂)₄-(4-MeO-Ph) H HH H 5-1353 H H Me 2 —CO—(CH₂)₄-(4-EtO-Ph) H H H H 5-1354 H H Me 2—CO—(CH₂)₄-(4-MeS-Ph) H H H H 5-1355 H H Me 2 —CO—(CH₂)₄-(4-cHx-Ph) H HH H 5-1356 H H Me 2 —CO—(CH₂)₄-(4-Ph-Ph) H H H H 5-1357 H H Me 2—CO—(CH₂)₅-cHx H H H H 5-1358 H Me Me 2 —CO—(CH₂)₅-cHx H H H H 5-1359CO₂Me H Me 2 —CO—(CH₂)₅-cHx H H H H 5-1360 CO₂Et H Me 2 —CO—(CH₂)₅-cHx HH H H 5-1361 H H Me 2 —CO—(CH₂)₅-(4-F-cHx) H H H H 5-1362 H H Me 2—CO—(CH₂)₅-(4-Me-cHx) H H H H 5-1363 H H Me 2 —CO—(CH₂)₅-(4-Et-cHx) H HH H 5-1364 H H Me 2 —CO—(CH₂)₅-(4-CF₃-cHx) H H H H 5-1365 H H Me 2—CO—(CH₂)₅-(4-MeO-cHx) H H H H 5-1366 H H Me 2 —CO—(CH₂)₅-(4-EtO-cHx) HH H H 5-1367 H H Me 2 —CO—(CH₂)₅-(4-MeS-cHx) H H H H 5-1368 H H Me 2—CO—(CH₂)₅-(4-cHx-cHx) H H H H 5-1369 H H Me 2 —CO—(CH₂)₅-(4-Ph-cHx) H HH H 5-1370 H H Me 2 —CO—(CH₂)₅-Ph H H H H 5-1371 H Me Me 2 —CO—(CH₂)₅-PhH H H H 5-1372 CO₂Me H Me 2 —CO—(CH₂)₅-Ph H H H H 5-1373 CO₂Et H Me 2—CO—(CH₂)₅-Ph H H H H 5-1374 H H Me 2 —CO—(CH₂)₅-(4-F-Ph) H H H H 5-1375H H Me 2 —CO—(CH₂)₅-(4-Me-Ph) H H H H 5-1376 H H Me 2—CO—(CH₂)₅-(4-Et-Ph) H H H H 5-1377 H H Me 2 —CO—(CH₂)₅-(4-CF₃-Ph) H H HH 5-1378 H H Me 2 —CO—(CH₂)₅-(4-MeO-Ph) H H H H 5-1379 H H Me 2—CO—(CH₂)₅-(4-EtO-Ph) H H H H 5-1380 H H Me 2 —CO—(CH₂)₅-(4-MeS-Ph) H HH H 5-1381 H H Me 2 —CO—(CH₂)₅-(4-cHx-Ph) H H H H 5-1382 H H Me 2—CO—(CH₂)₅-(4-Ph-Ph) H H H H 5-1383 H H Me 2 —CO—(CH₂)₆-cHx H H H H5-1384 H H Me 2 —CO—(CH₂)₆-Ph H H H H 5-1385 H H Me 2 —CO—(CH₂)₇-cHx H HH H 5-1386 H H Me 2 —CO—(CH₂)₇-Ph H H H H 5-1387 H H Me 2—CO—(CH₂)₂—O-cHx H H H H 5-1388 H Me Me 2 —CO—(CH₂)₂—O-cHx H H H H5-1389 CO₂Me H Me 2 —CO—(CH₂)₂—O-cHx H H H H 5-1390 CO₂Et H Me 2—CO—(CH₂)₂—O-cHx H H H H 5-1391 H H Me 2 —CO—(CH₂)₂—O-(4-F-cHx) H H H H5-1392 H H Me 2 —CO—(CH₂)₂—O-(4-Me-cHx) H H H H 5-1393 H H Me 2—CO—(CH₂)₂—O-(4-Et-cHx) H H H H 5-1394 H H Me 2 —CO—(CH₂)₂—O-(4-CF₃-cHx)H H H H 5-1395 H H Me 2 —CO—(CH₂)₂—O-(4-MeO-cHx) H H H H 5-1396 H H Me 2—CO—(CH₂)₂—O-(4-EtO-cHx) H H H H 5-1397 H H Me 2—CO—(CH₂)₂—O-(4-MeS-cHx) H H H H 5-1398 H H Me 2—CO—(CH₂)₂—O-(4-cHx-cHx) H H H H 5-1399 H H Me 2 —CO—(CH₂)₂—O-(4-Ph-cHx)H H H H 5-1400 H H Me 2 —CO—(CH₂)₂—O-Ph H H H H 5-1401 H Me Me 2—CO—(CH₂)₂—O-Ph H H H H 5-1402 CO₂Me H Me 2 —CO—(CH₂)₂—O-Ph H H H H5-1403 CO₂Et H Me 2 —CO—(CH₂)₂—O-Ph H H H H 5-1404 H H Me 2—CO—(CH₂)₂—O-(4-F-Ph) H H H H 5-1405 H H Me 2 —CO—(CH₂)₂—O-(4-Me-Ph) H HH H 5-1406 H H Me 2 —CO—(CH₂)₂—O-(4-Et-Ph) H H H H 5-1407 H H Me 2—CO—(CH₂)₂—O-(4-CF₃-Ph) H H H H 5-1408 H H Me 2 —CO—(CH₂)₂—O-(4-MeO-Ph)H H H H 5-1409 H H Me 2 —CO—(CH₂)₂—O-(4-EtO-Ph) H H H H 5-1410 H H Me 2—CO—(CH₂)₂—O-(4-MeS-Ph) H H H H 5-1411 H H Me 2 —CO—(CH₂)₂—O-(4-cHx-Ph)H H H H 5-1412 H H Me 2 —CO—(CH₂)₂—O-(4-Ph-Ph) H H H H 5-1413 H H Me 2—CO—(CH₂)₃—O-cPn H H H H 5-1414 H H Me 2 —CO—(CH₂)₃—O-cHx H H H H 5-1415H H Me 2 —CO—(CH₂)₃—O-cHx Me H H H 5-1416 H H Me 2 —CO—(CH₂)₃—O-cHx H MeH H 5-1417 H H Me 2 —CO—(CH₂)₃—O-cHx F H H H 5-1418 H H Me 2—CO—(CH₂)₃—O-cHx H F H H 5-1419 H Me Me 2 —CO—(CH₂)₃—O-cHx H H H H5-1420 CO₂Me H Me 2 —CO—(CH₂)₃—O-cHx H H H H 5-1421 CO₂Et H Me 2—CO—(CH₂)₃—O-cHx H H H H 5-1422 H H Me 2 —CO—(CH₂)₃—O-(3-F-cHx) H H H H5-1423 H H Me 2 —CO—(CH₂)₃—O-(4-F-cHx) H H H H 5-1424 H H Me 2—CO—(CH₂)₃—O-(4-Cl-cHx) H H H H 5-1425 H H Me 2 —CO—(CH₂)₃—O-(4-Br-cHx)H H H H 5-1426 H H Me 2 —CO—(CH₂)₃—O-(3-Me-cHx) H H H H 5-1427 H H Me 2—CO—(CH₂)₃—O-(4-Me-cHx) H H H H 5-1428 H H Me 2 —CO—(CH₂)₃—O-(3-Et-cHx)H H H H 5-1429 H H Me 2 —CO—(CH₂)₃—O-(4-Et-cHx) H H H H 5-1430 H H Me 2—CO—(CH₂)₃—O-(3-Pr-cHx) H H H H 5-1431 H H Me 2 —CO—(CH₂)₃—O-(4-Pr-cHx)H H H H 5-1432 H H Me 2 —CO—(CH₂)₃—O-(4-iPr-cHx) H H H H 5-1433 H H Me 2—CO—(CH₂)₃—O-(3-Bu-cHx) H H H H 5-1434 H H Me 2 —CO—(CH₂)₃—O-(4-Bu-cHx)H H H H 5-1435 H H Me 2 —CO—(CH₂)₃—O-(3-CF₃-cHx) H H H H 5-1436 H H Me 2—CO—(CH₂)₃—O-(4-CF₃-cHx) H H H H 5-1437 H H Me 2—CO—(CH₂)₃—O-(3-MeO-cHx) H H H H 5-1438 H H Me 2—CO—(CH₂)₃—O-(4-MeO-cHx) H H H H 5-1439 H H Me 2—CO—(CH₂)₃—O-(3-EtO-cHx) H H H H 5-1440 H H Me 2—CO—(CH₂)₃—O-(4-EtO-cHx) H H H H 5-1441 H H Me 2—CO—(CH₂)₃—O-(3-PrO-cHx) H H H H 5-1442 H H Me 2—CO—(CH₂)₃—O-(4-PrO-cHx) H H H H 5-1443 H H Me 2—CO—(CH₂)₃—O-(3-iPrO-cHx) H H H H 5-1444 H H Me 2—CO—(CH₂)₃—O-(4-iPrO-cHx) H H H H 5-1445 H H Me 2—CO—(CH₂)₃—O-[3-(2-Et-PrO)cHx] H H H H 5-1446 H H Me 2—CO—(CH₂)₃—O-[4-(2-Et-PrO)cHx] H H H H 5-1447 H H Me 2—CO—(CH₂)₃—O-(3-iBuO-cHx) H H H H 5-1448 H H Me 2—CO—(CH₂)₃—O-(4-iBuO-cHx) H H H H 5-1449 H H Me 2—CO—(CH₂)₃—O-(3-MeS-cHx) H H H H 5-1450 H H Me 2—CO—(CH₂)₃—O-(4-MeS-cHx) H H H H 5-1451 H H Me 2—CO—(CH₂)₃—O-(3-EtS-cHx) H H H H 5-1452 H H Me 2—CO—(CH₂)₃—O-(4-EtS-cHx) H H H H 5-1453 H H Me 2—CO—(CH₂)₃—O-(3-PrS-cHx) H H H H 5-1454 H H Me 2—CO—(CH₂)₃—O-(4-PrS-cHx) H H H H 5-1455 H H Me 2—CO—(CH₂)₃—O-(3-iPrS-cHx) H H H H 5-1456 H H Me 2—CO—(CH₂)₃—O-(4-iPrS-cHx) H H H H 5-1457 H H Me 2—CO—(CH₂)₃—O-[3-(2-Et-PrS)cHx] H H H H 5-1458 H H Me 2—CO—(CH₂)₃—O-[4-(2-Et-PrS)cHx] H H H H 5-1459 H H Me 2—CO—(CH₂)₃—O-(3-iBuS-cHx) H H H H 5-1460 H H Me 2—CO—(CH₂)₃—O-(4-iBuS-cHx) H H H H 5-1461 H H Me 2—CO—(CH₂)₃—O-(3-cHx-cHx) H H H H 5-1462 H H Me 2—CO—(CH₂)₃—O-(4-cHx-cHx) H H H H 5-1463 H H Me 2 —CO—(CH₂)₃—O-(3-Ph-cHx)H H H H 5-1464 H H Me 2 —CO—(CH₂)₃—O-(4-Ph-cHx) H H H H 5-1465 H H Me 2—CO—(CH₂)₃—O-(2,4-diMe-cHx) H H H H 5-1466 H H Me 2—CO—(CH₂)₃—O-(3,4-diMe-cHx) H H H H 5-1467 H H Me 2—CO—(CH₂)₃—O-(3,5-diMe-cHx) H H H H 5-1468 H H Me 2 —CO—(CH₂)₃—O-Ph H HH H 5-1469 H H Me 2 —CO—(CH₂)₃—O-Ph Me H H H 5-1470 H H Me 2—CO—(CH₂)₃—O-Ph H Me H H 5-1471 H H Me 2 —CO—(CH₂)₃—O-Ph F H H H 5-1472H H Me 2 —CO—(CH₂)₃—O-Ph H F H H 5-1473 H Me Me 2 —CO—(CH₂)₃—O-Ph H H HH 5-1474 CO₂Me H Me 2 —CO—(CH₂)₃—O-Ph H H H H 5-1475 CO₂Et H Me 2—CO—(CH₂)₃—O-Ph H H H H 5-1476 H H Me 2 —CO—(CH₂)₃—O-(3-F-Ph) H H H H5-1477 H H Me 2 —CO—(CH₂)₃—O-(4-F-Ph) H H H H 5-1478 H H Me 2—CO—(CH₂)₃—O-(4-Cl-Ph) H H H H 5-1479 H H Me 2 —CO—(CH₂)₃—O-(4-Br-Ph) HH H H 5-1480 H H Me 2 —CO—(CH₂)₃—O-(3-Me-Ph) H H H H 5-1481 H H Me 2—CO—(CH₂)₃—O-(4-Me-Ph) H H H H 5-1482 H H Me 2 —CO—(CH₂)₃—O-(3-Et-Ph) HH H H 5-1483 H H Me 2 —CO—(CH₂)₃—O-(4-Et-Ph) H H H H 5-1484 H H Me 2—CO—(CH₂)₃—O-(3-Pr-Ph) H H H H 5-1485 H H Me 2 —CO—(CH₂)₃—O-(4-Pr-Ph) HH H H 5-1486 H H Me 2 —CO—(CH₂)₃—O-(3-iPr-Ph) H H H H 5-1487 H H Me 2—CO—(CH₂)₃—O-(4-iPr-Ph) H H H H 5-1488 H H Me 2 —CO—(CH₂)₃—O-(3-Bu-Ph) HH H H 5-1489 H H Me 2 —CO—(CH₂)₃—O-(4-Bu-Ph) H H H H 5-1490 H H Me 2—CO—(CH₂)₃—O-(3-CF₃-Ph) H H H H 5-1491 H H Me 2 —CO—(CH₂)₃—O-(4-CF₃-Ph)H H H H 5-1492 H H Me 2 —CO—(CH₂)₃—O-(3-MeO-Ph) H H H H 5-1493 H H Me 2—CO—(CH₂)₃—O-(4-MeO-Ph) H H H H 5-1494 H H Me 2 —CO—(CH₂)₃—O-(3-EtO-Ph)H H H H 5-1495 H H Me 2 —CO—(CH₂)₃—O-(4-EtO-Ph) H H H H 5-1496 H H Me 2—CO—(CH₂)₃—O-(3-PrO-Ph) H H H H 5-1497 H H Me 2 —CO—(CH₂)₃—O-(4-PrO-Ph)H H H H 5-1498 H H Me 2 —CO—(CH₂)₃—O-(3-iPrO-Ph) H H H H 5-1499 H H Me 2—CO—(CH₂)₃—O-(4-iPrO-Ph) H H H H 5-1500 H H Me 2—CO—(CH₂)₃—O-[3-(2-Et-PrO)-Ph] H H H H 5-1501 H H Me 2—CO—(CH₂)₃—O-[4-(2-Et-PrO)-Ph] H H H H 5-1502 H H Me 2—CO—(CH₂)₃—O-(3-iBuO-Ph) H H H H 5-1503 H H Me 2—CO—(CH₂)₃—O-(4-iBuO-Ph) H H H H 5-1504 H H Me 2 —CO—(CH₂)₃—O-(3-MeS-Ph)H H H H 5-1505 H H Me 2 —CO—(CH₂)₃—O-(4-MeS-Ph) H H H H 5-1506 H H Me 2—CO—(CH₂)₃—O-(3-EtS-Ph) H H H H 5-1507 H H Me 2 —CO—(CH₂)₃—O-(4-EtS-Ph)H H H H 5-1508 H H Me 2 —CO—(CH₂)₃—O-(3-PrS-Ph) H H H H 5-1509 H H Me 2—CO—(CH₂)₃—O-(4-PrS-Ph) H H H H 5-1510 H H Me 2 —CO—(CH₂)₃—O-(3-iPrS-Ph)H H H H 5-1511 H H Me 2 —CO—(CH₂)₃—O-(4-iPrS-Ph) H H H H 5-1512 H H Me 2—CO—(CH₂)₃—O-[3-(2-Et-PrS)-Ph] H H H H 5-1513 H H Me 2—CO—(CH₂)₃—O-[4-(2-Et-PrS)-Ph] H H H H 5-1514 H H Me 2—CO—(CH₂)₃—O-(3-iBuS-Ph) H H H H 5-1515 H H Me 2—CO—(CH₂)₃—O-(4-iBuS-Ph) H H H H 5-1516 H H Me 2 —CO—(CH₂)₃—O-(3-cHx-Ph)H H H H 5-1517 H H Me 2 —CO—(CH₂)₃—O-(4-cHx-Ph) H H H H 5-1518 H H Me 2—CO—(CH₂)₃—O-(3-Ph-Ph) H H H H 5-1519 H H Me 2 —CO—(CH₂)₃—O-(4-Ph-Ph) HH H H 5-1520 H H Me 2 —CO—(CH₂)₃—O-(2,4-diMe-Ph) H H H H 5-1521 H H Me 2—CO—(CH₂)₃—O-(3,4-diMe-Ph) H H H H 5-1522 H H Me 2—CO—(CH₂)₃—O-(3,5-diMe-Ph) H H H H 5-1523 H H Me 2 —CO—(CH₂)₄—O-cHx H HH H 5-1524 H H Me 2 —CO—(CH₂)₄—O-Ph H H H H 5-1525 H H Me 2—CO—(CH₂)₅—O-cHx H H H H 5-1526 H H Me 2 —CO—(CH₂)₅—O-Ph H H H H 5-1527H H Me 2 —CO—(CH₂)₂—OCH₂-cHx H H H H 5-1528 H Me Me 2—CO—(CH₂)₂—OCH₂-cHx H H H H 5-1529 CO₂Me H Me 2 —CO—(CH₂)₂—OCH₂-cHx H HH H 5-1530 CO₂Et H Me 2 —CO—(CH₂)₂—OCH₂-cHx H H H H 5-1531 H H Me 2—CO—(CH₂)₂—OCH₂-(4-F-cHx) H H H H 5-1532 H H Me 2—CO—(CH₂)₂—OCH₂-(4-Me-cHx) H H H H 5-1533 H H Me 2—CO—(CH₂)₂—OCH₂-(4-Et-cHx) H H H H 5-1534 H H Me 2—CO—(CH₂)₂—OCH₂-(4-CF₃-cHx) H H H H 5-1535 H H Me 2—CO—(CH₂)₂—OCH₂-(4-MeO-cHx) H H H H 5-1536 H H Me 2—CO—(CH₂)₂—OCH₂-(4-EtO-cHx) H H H H 5-1537 H H Me 2—CO—(CH₂)₂—OCH₂-(4-MeS-cHx) H H H H 5-1538 H H Me 2—CO—(CH₂)₂—OCH₂-(4-cHx-cHx) H H H H 5-1539 H H Me 2—CO—(CH₂)₂—OCH₂-(4-Ph-cHx) H H H H 5-1540 H H Me 2 —CO—(CH₂)₂—OCH₂-Ph HH H H 5-1541 H Me Me 2 —CO—(CH₂)₂—OCH₂-Ph H H H H 5-1542 CO₂Me H Me 2—CO—(CH₂)₂—OCH₂-Ph H H H H 5-1543 CO₂Et H Me 2 —CO—(CH₂)₂—OCH₂-Ph H H HH 5-1544 H H Me 2 —CO—(CH₂)₂—OCH₂-(4-F-Ph) H H H H 5-1545 H H Me 2—CO—(CH₂)₂—OCH₂-(4-Me-Ph) H H H H 5-1546 H H Me 2—CO—(CH₂)₂—OCH₂-(4-Et-Ph) H H H H 5-1547 H H Me 2—CO—(CH₂)₂—OCH₂-(4-CF₃-Ph) H H H H 5-1548 H H Me 2—CO—(CH₂)₂—OCH₂-(4-MeO-Ph) H H H H 5-1549 H H Me 2—CO—(CH₂)₂—OCH₂-(4-EtO-Ph) H H H H 5-1550 H H Me 2—CO—(CH₂)₂—OCH₂-(4-MeS-Ph) H H H H 5-1551 H H Me 2—CO—(CH₂)₂—OCH₂-(4-cHx-Ph) H H H H 5-1552 H H Me 2—CO—(CH₂)₂—OCH₂-(4-Ph-Ph) H H H H 5-1553 H H Me 2—CO—(CH₂)₃—OCH₂—CH₂-cPn H H H H 5-1554 H H Me 2 —CO—(CH₂)₃—OCH₂-cHx H HH H 5-1555 H H Me 2 —CO—(CH₂)₃—OCH₂-cHx Me H H H 5-1556 H H Me 2—CO—(CH₂)₃—OCH₂-cHx H Me H H 5-1557 H H Me 2 —CO—(CH₂)₃—OCH₂-cHx F H H H5-1558 H H Me 2 —CO—(CH₂)₃—OCH₂-cHx H F H H 5-1559 H Me Me 2—CO—(CH₂)₃—OCH₂-cHx H H H H 5-1560 COMe H Me 2 —CO—(CH₂)₃—OCH₂-cHx H H HH 5-1561 CO₂Et H Me 2 —CO—(CH₂)₃—OCH₂-cHx H H H H 5-1562 H H Me 2—CO—(CH₂)₃—OCH₂-(3-F-cHx) H H H H 5-1563 H H Me 2—CO—(CH₂)₃—OCH₂-(4-F-cHx) H H H H 5-1564 H H Me 2—CO—(CH₂)₃—OCH₂-(4-Cl-cHx) H H H H 5-1565 H H Me 2—CO—(CH₂)₃—OCH₂-(4-Br-cHx) H H H H 5-1566 H H Me 2—CO—(CH₂)₃—OCH₂-(3-Me-cHx) H H H H 5-1567 H H Me 2—CO—(CH₂)₃—OCH₂-(4-Me-cHx) H H H H 5-1568 H H Me 2—CO—(CH₂)₃—OCH₂-(3-Et-cHx) H H H H 5-1569 H H Me 2—CO—(CH₂)₃—OCH₂-(4-Et-cHx) H H H H 5-1570 H H Me 2—CO—(CH₂)₃—OCH₂-(3-Pr-cHx) H H H H 5-1571 H H Me 2—CO—(CH₂)₃—OCH₂-(4-Pr-cHx) H H H H 5-1572 H H Me 2—CO—(CH₂)₃—OCH₂-(4-iPr-cHx) H H H H 5-1573 H H Me 2—CO—(CH₂)₃—OCH₂-(3-Bu-cHx) H H H H 5-1574 H H Me 2—CO—(CH₂)₃—OCH₂-(4-Bu-cHx) H H H H 5-1575 H H Me 2—CO—(CH₂)₃—OCH₂-(3-CF₃-cHx) H H H H 5-1576 H H Me 2—CO—(CH₂)₃—OCH₂-(4-CF₃-cHx) H H H H 5-1577 H H Me 2—CO—(CH₂)₃—OCH₂-(3-MeO-cHx) H H H H 5-1578 H H Me 2—CO—(CH₂)₃—OCH₂-(4-MeO-cHx) H H H H 5-1579 H H Me 2—CO—(CH₂)₃—OCH₂-(3-EtO-cHx) H H H H 5-1580 H H Me 2—CO—(CH₂)₃—OCH₂-(4-EtO-cHx) H H H H 5-1581 H H Me 2—CO—(CH₂)₃—OCH₂-(3-PrO-cHx) H H H H 5-1582 H H Me 2—CO—(CH₂)₃—OCH₂-(4-PrO-cHx) H H H H 5-1583 H H Me 2—CO—(CH₂)₃—OCH₂-(3-iPrO-cHx) H H H H 5-1584 H H Me 2—CO—(CH₂)₃—OCH₂-(4-iPrO-cHx) H H H H 5-1585 H H Me 2—CO—(CH₂)₃—OCH₂-[3-(2-Et-PrO)cHx] H H H H 5-1586 H H Me 2—CO—(CH₂)₃—OCH₂-[4-(2-Et-PrO)cHx] H H H H 5-1587 H H Me 2—CO—(CH₂)₃—OCH₂-(3-iBuO-cHx) H H H H 5-1588 H H Me 2—CO—(CH₂)₃—OCH₂-(4-iBuO-cHx) H H H H 5-1589 H H Me 2—CO—(CH₂)₃—OCH₂-(3-MeS-cHx) H H H H 5-1590 H H Me 2—CO—(CH₂)₃—OCH₂-(4-MeS-cHx) H H H H 5-1591 H H Me 2—CO—(CH₂)₃—OCH₂-(3-EtS-cHx) H H H H 5-1592 H H Me 2—CO—(CH₂)₃—OCH₂-(4-EtS-cHx) H H H H 5-1593 H H Me 2—CO—(CH₂)₃—OCH₂-(3-PrS-cHx) H H H H 5-1594 H H Me 2—CO—(CH₂)₃—OCH₂-(4-PrS-cHx) H H H H 5-1595 H H Me 2—CO—(CH₂)₃—OCH₂-(3-iPrS-cHx) H H H H 5-1596 H H Me 2—CO—(CH₂)₃—OCH₂-(4-iPrS-cHx) H H H H 5-1597 H H Me 2—CO—(CH₂)₃—OCH₂-[3-(2-Et-PrS)cHx] H H 5-1598 H H Me 2—CO—(CH₂)₃—OCH₂-[4-(2-Et-PrS)cHx] H H 5-1599 H H Me 2—CO—(CH₂)₃—OCH₂-(3-iBuS-cHx) H H H H 5-1600 H H Me 2—CO—(CH₂)₃—OCH₂-(4-iBuS-cHx) H H H H 5-1601 H H Me 2—CO—(CH₂)₃—OCH₂-(3-cHx-cHx) H H H H 5-1602 H H Me 2—CO—(CH₂)₃—OCH₂-(4-cHx-cHx) H H H H 5-1603 H H Me 2—CO—(CH₂)₃—OCH₂-(3-Ph-cHx) H H H H 5-1604 H H Me 2—CO—(CH₂)₃—OCH₂-(4-Ph-cHx) H H H H 5-1605 H H Me 2—CO—(CH₂)₃—OCH₂-(2,4-diMe-cHx) H H H H 5-1606 H H Me 2—CO—(CH₂)₃—OCH₂-(3,4-diMe-cHx) H H H H 5-1607 H H Me 2—CO—(CH₂)₃—OCH₂-(3,5-diMe-cHx) H H H H 5-1608 H H Me 2—CO—(CH₂)₃—OCH₂-Ph H H H H 5-1609 H H Me 2 —CO—(CH₂)₃—OCH₂-Ph Me H H H5-1610 H H Me 2 —CO—(CH₂)₃—OCH₂-Ph H Me H H 5-1611 H H Me 2—CO—(CH₂)₃—OCH₂-Ph F H H H 5-1612 H H Me 2 —CO—(CH₂)₃—OCH₂-Ph H F H H5-1613 H Me Me 2 —CO—(CH₂)₃—OCH₂-Ph H H H H 5-1614 CO₂Me H Me 2—CO—(CH₂)₃—OCH₂-Ph H H H H 5-1615 CO₂Me H Me 2 —CO—(CH₂)₃—OCH₂-Ph H H HH 5-1616 H H Me 2 —CO—(CH₂)₃—OCH₂-(3-F-Ph) H H H H 5-1617 H H Me 2—CO—(CH₂)₃—OCH₂-(4-F-Ph) H H H H 5-1618 H H Me 2—CO—(CH₂)₃—OCH₂-(4-Cl-Ph) H H H H 5-1619 H H Me 2—CO—(CH₂)₃—OCH₂-(4-Br-Ph) H H H H 5-1620 H H Me 2—CO—(CH₂)₃—OCH₂-(3-Me-Ph) H H H H 5-1621 H H Me 2—CO—(CH₂)₃—OCH₂-(4-Me-Ph) H H H H 5-1622 H H Me 2—CO—(CH₂)₃—OCH₂-(3-Et-Ph) H H H H 5-1623 H H Me 2—CO—(CH₂)₃—OCH₂-(4-Et-Ph) H H H H 5-1624 H H Me 2—CO—(CH₂)₃—OCH₂-(3-Pr-Ph) H H H H 5-1625 H H Me 2—CO—(CH₂)₃—OCH₂-(4-Pr-Ph) H H H H 5-1626 H H Me 2—CO—(CH₂)₃—OCH₂-(3-iPr-Ph) H H H H 5-1627 H H Me 2—CO—(CH₂)₃—OCH₂-(4-iPr-Ph) H H H H 5-1628 H H Me 2—CO—(CH₂)₃—OCH₂-(3-Bu-Ph) H H H H 5-1629 H H Me 2—CO—(CH₂)₃—OCH₂-(4-Bu-Ph) H H H H 5-1630 H H Me 2—CO—(CH₂)₃—OCH₂-(3-CF₃-Ph) H H H H 5-1631 H H Me 2—CO—(CH₂)₃—OCH₂-(4-CF₃-Ph) H H H H 5-1632 H H Me 2—CO—(CH₂)₃—OCH₂-(3-MeO-Ph) H H H H 5-1633 H H Me 2—CO—(CH₂)₃—OCH₂-(4-MeO-Ph) H H H H 5-1634 H H Me 2—CO—(CH₂)₃—OCH₂-(3-EtO-Ph) H H H H 5-1635 H H Me 2—CO—(CH₂)₃—OCH₂-(4-EtO-Ph) H H H H 5-1636 H H Me 2—CO—(CH₂)₃—OCH₂-(3-PrO-Ph) H H H H 5-1637 H H Me 2—CO—(CH₂)₃—OCH₂-(4-PrO-Ph) H H H H 5-1638 H H Me 2—CO—(CH₂)₃—OCH₂-(3-iPrO-Ph) H H H H 5-1639 H H Me 2—CO—(CH₂)₃—OCH₂-(4-iPrO-Ph) H H H H 5-1640 H H Me 2—CO—(CH₂)₃—OCH₂-[3-(2-Et-PrO)Ph] H H H H 5-1641 H H Me 2—CO—(CH₂)₃—OCH₂-[4-(2-Et-PrO)Ph] H H H H 5-1642 H H Me 2—CO—(CH₂)₃—OCH₂-(3-iBuO-Ph) H H H H 5-1643 H H Me 2—CO—(CH₂)₃—OCH₂-(4-iBuO-Ph) H H H H 5-1644 H H Me 2—CO—(CH₂)₃—OCH₂-(3-MeS-Ph) H H H H 5-1645 H H Me 2—CO—(CH₂)₃—OCH₂-(4-MeS-Ph) H H H H 5-1646 H H Me 2—CO—(CH₂)₃—OCH₂-(3-EtS-Ph) H H H H 5-1647 H H Me 2—CO—(CH₂)₃—OCH₂-(4-EtS-Ph) H H H H 5-1648 H H Me 2—CO—(CH₂)₃—OCH₂-(3-PrS-Ph) H H H H 5-1649 H H Me 2—CO—(CH₂)₃—OCH₂-(4-PrS-Ph) H H H H 5-1650 H H Me 2—CO—(CH₂)₃—OCH₂-(3-iPrS-Ph) H H H H 5-1651 H H Me 2—CO—(CH₂)₃—OCH₂-(4-iPrS-PH) H H H H 5-1652 H H Me 2—CO—(CH₂)₃—OCH₂-[3-(2-Et-PrS)Ph] H H H H 5-1653 H H Me 2—CO—(CH₂)₃—OCH₂-[4-(2-Et-PrS)Ph] H H H H 5-1654 H H Me 2—CO—(CH₂)₃—OCH₂-(3-iBuS-Ph) H H H H 5-1655 H H Me 2—CO—(CH₂)₃—OCH₂-(4-iBuS-Ph) H H H H 5-1656 H H Me 2—CO—(CH₂)₃—OCH₂-(3-cHx-Ph) H H H H 5-1657 H H Me 2—CO—(CH₂)₃—OCH₂-(4-cHx-Ph) H H H H 5-1658 H H Me 2—CO—(CH₂)₃—OCH₂-(3-Ph-Ph) H H H H 5-1659 H H Me 2—CO—(CH₂)₃—OCH₂-(4-Ph-Ph) H H H H 5-1660 H H Me 2—CO—(CH₂)₃—OCH₂-(2,4-diMe-Ph) H H H H 5-1661 H H Me 2—CO—(CH₂)₃—OCH₂-(3,4-diMe-Ph) H H H H 5-1662 H H Me 2—CO—(CH₂)₃—OCH₂-(3,5-diMe-Ph) H H H H 5-1663 H H Me 2—CO—(CH₂)₄—OCH₂-cHx H H H H 5-1664 H H Me 2 —CO—(CH₂)₄—OCH₂-Ph H H H H5-1665 H H Me 2 —CO—(CH₂)₅—OCH₂-cHx H H H H 5-1666 H H Me 2—CO—(CH₂)₅—OCH₂-Ph H H H H 5-1667 H H Me 2 —CH(OH)—CH₂-cHx H H H H5-1668 H H Me 2 —CH(OH)—CH₂-Ph H H H H 5-1669 H H Me 2—CH(OH)—(CH₂)₂-cHx H H H H 5-1670 H H Me 2 —CH(OH)—(CH₂)₂-Ph H H H H5-1671 H H Me 2 —CH(OH)—(CH₂)₃-cHx H H H H 5-1672 H H Me 2—CH(OH)—(CH₂)₃-Ph H H H H 5-1673 H H Me 2 —CH(OH)—(CH₂)₄-cHx H H H H5-1674 H Me Me 2 —CH(OH)—(CH₂)₄-cHx H H H H 5-1675 CO₂Me H Me 2—CH(OH)—(CH₂)₄-cHx H H H H 5-1676 CO₂Et H Me 2 —CH(OH)—(CH₂)₄-cHx H H HH 5-1677 H H Me 2 —CH(OH)—(CH₂)₄-(4-F-cHx) H H H H 5-1678 H H Me 2—CH(OH)—(CH₂)₄-(4-Me-cHx) H H H H 5-1679 H H Me 2—CH(OH)—(CH₂)₄-(4-Et-cHx) H H H H 5-1680 H H Me 2—CH(OH)—(CH₂)₄-(4-CF₃-cHx) H H H H 5-1681 H H Me 2—CH(OH)—(CH₂)₄-(4-MeO-cHx) H H H H 5-1682 H H Me 2—CH(OH)—(CH₂)₄-(4-EtO-cHx) H H H H 5-1683 H H Me 2—CH(OH)—(CH₂)₄-(4-MeS-cHx) H H H H 5-1684 H H Me 2—CH(OH)—(CH₂)₄-(4-cHx-cHx) H H H H 5-1685 H H Me 2—CH(OH)—(CH₂)₄-(4-Ph-cHx) H H H H 5-1686 H H Me 2 —CH(OH)—(CH₂)₄-Ph H HH H 5-1687 H Me Me 2 —CH(OH)—(CH₂)₄-Ph H H H H 5-1688 CO₂Me H Me 2—CH(OH)—(CH₂)₄-Ph H H H H 5-1689 CO₂Et H Me 2 —CH(OH)—(CH₂)₄-Ph H H H H5-1690 H H Me 2 —CH(OH)—(CH₂)₄-(4-F-Ph) H H H H 5-1691 H H Me 2—CH(OH)—(CH₂)₄-(4-Me-Ph) H H H H 5-1692 H H Me 2—CH(OH)—(CH₂)₄-(4-Et-Ph) H H H H 5-1693 H H Me 2—CH(OH)—(CH₂)₄-(4-CF₃-Ph) H H H H 5-1694 H H Me 2—CH(OH)—(CH₂)₄-(4-MeO-Ph) H H H H 5-1695 H H Me 2—CH(OH)—(CH₂)₄-(4-EtO-Ph) H H H H 5-1696 H H Me 2—CH(OH)—(CH₂)₄-(4-MeS-Ph) H H H H 5-1697 H H Me 2—CH(OH)—(CH₂)₄-(4-cHx-Ph) H H H H 5-1698 H H Me 2—CH(OH)—(CH₂)₄-(4-Ph-Ph) H H H H 5-1699 H H Me 2 —CH(OH)—(CH₂)₅-cHx H HH H 5-1700 H Me Me 2 —CH(OH)—(CH₂)₅-cHx H H H H 5-1701 CO₂Me H Me 2—CH(OH)—(CH₂)₅-cHx H H H H 5-1702 CO₂Et H Me 2 —CH(OH)—(CH₂)₅-cHx H H HH 5-1703 H H Me 2 —CH(OH)—(CH₂)₅-(4-F-cHx) H H H H 5-1704 H H Me 2—CH(OH)—(CH₂)₅-(4-Me-cHx) H H H H 5-1705 H H Me 2—CH(OH)—(CH₂)₅-(4-Et-cHx) H H H H 5-1706 H H Me 2—CH(OH)—(CH₂)₅-(4-CF₃-cHx) H H H H 5-1707 H H Me 2—CH(OH)—(CH₂)₅-(4-MeO-cHx) H H H H 5-1708 H H Me 2—CH(OH)—(CH₂)₅-(4-EtO-cHx) H H H H 5-1709 H H Me 2—CH(OH)—(CH₂)₅-(4-MeS-cHx) H H H H 5-1710 H H Me 2—CH(OH)—(CH₂)₅-(4-cHx-cHx) H H H H 5-1711 H H Me 2—CH(OH)—(CH₂)₅-(4-Ph-cHx) H H H H 5-1712 H H Me 2 —CH(OH)—(CH₂)₅-Ph H HH H 5-1713 H Me Me 2 —CH(OH)—(CH₂)₅-Ph H H H H 5-1714 CO₂Me H Me 2—CH(OH)—(CH₂)₅-Ph H H H H 5-1715 CO₂Et H Me 2 —CH(OH)—(CH₂)₅-Ph H H H H5-1716 H H Me 2 —CH(OH)—(CH₂)₅-(4-F-Ph) H H H H 5-17.17 H H Me 2—CH(OH)—(CH₂)₅-(4-Me-Ph) H H H H 5-1718 H H Me 2—CH(OH)—(CH₂)₅-(4-Et-Ph) H H H H 5-1719 H H Me 2—CH(OH)—(CH₂)₅-(4-CF₃-Ph) H H H H 5-1720 H H Me 2—CH(OH)—(CH₂)₅-(4-MeO-Ph) H H H H 5-1721 H H Me 2—CH(OH)—(CH₂)₅-(4-EtO-Ph) H H H H 5-1722 H H Me 2—CH(OH)—(CH₂)₅-(4-MeS-Ph) H H H H 5-1723 H H Me 2—CH(OH)—(CH₂)₅-(4-cHx-Ph) H H H H 5-1724 H H Me 2—CH(OH)—(CH₂)₅-(4-Ph-Ph) H H H H 5-1725 H H Me 2 —CH(OH)—(CH₂)₆-cHx H HH H 5-1726 H H Me 2 —CH(OH)—(CH₂)₆-Ph H H H H 5-1727 H H Me 2—CH(OH)—(CH₂)₇-cHx H H H H 5-1728 H H Me 2 —CH(OH)—(CH₂)₇-Ph H H H H5-1729 H H Me 2 -4-(cHx-CH₂O)Ph H H H H 5-1730 H Me Me 2 -4-(cHx-CH₂O)PhH H H H 5-1731 CO₂Me H Me 2 -4-(cHx-CH₂O)Ph H H H H 5-1732 CO₂Et H Me 2-4-(cHx-CH₂O)Ph H H H H 5-1733 H H Me 2 -4-(cHx-CH₂O)-2-F-Ph H H H H5-1734 H H Me 2 -4-(cHx-CH₂O)-3-F-Ph H H H H 5-1735 H H Me 2-4-(cHx-CH₂O)-2,3-diF-Ph H H H H 5-1736 H H Me 2 -4-(cHx-CH₂O)-2-Cl-Ph HH H H 5-1737 H H Me 2 -4-(cHx-CH₂O)-3-Cl-Ph H H H H 5-1738 H H Me 2-4-(cHx-CH₂O)-2,3-diCl-Ph H H H H 5-1739 H H Me 2 -4-(cHx-CH₂O)-2-Me-PhH H H H 5-1740 H H Me 2 -4-(cHx-CH₂O)-3-Me-Ph H H H H 5-1741 H H Me 2-4-(cHx-CH₂O)-2,3-diMe-Ph H H H H 5-1742 H H Me 2 -4-[cHx-(CH₂)₂O]Ph H HH H 5-1743 H H Me 2 -4-[cHx-(CH₂)₃O]Ph H H H H 5-1744 H H Me 2-(4-BzO-Ph) H H H H 5-1745 H Me Me 2 -(4-BzO-Ph) H H H H 5-1746 CO₂Me HMe 2 -(4-BzO-Ph) H H H H 5-1747 CO₂Et H Me 2 -(4-BzO-Ph) H H H H 5-1748H H Me 2 -(4-BzO-2-F-Ph) H H H H 5-1749 H H Me 2 -(4-BzO-3-F-Ph) H H H H5-1750 H H Me 2 -(4-BzO-2,3-diF-Ph) H H H H 5-1751 H H Me 2-(4-BzO-2-Cl-Ph) H H H H 5-1752 H H Me 2 -(4-BzO-3-Cl-Ph) H H H H 5-1753H H Me 2 -(4-BzO-2,3-diCl-Ph) H H H H 5-1754 H H Me 2 -(4-BzO-2-Me-Ph) HH H H 5-1755 H H Me 2 -(4-BzO-3-Me-Ph) H H H H 5-1756 H H Me 2-(4-BzO-2,3-diMe-Ph) H H H H 5-1757 H H Me 2 -4-[Ph-(CH₂)₂O]-Ph H H H H5-1758 H H Me 2 -4-[Ph-(CH₂)₃O]-Ph H H H H 5-1759 H H Et 2 —(CH₂)₃-cHx HH H H 5-1760 H H Et 2 —(CH₂)₃-Ph H H H H 5-1761 H H Et 2 —(CH₂)₄-cHx H HH H 5-1762 H H Et 2 —(CH₂)₄-Ph H H H H 5-1763 H H Et 2 —(CH₂)₅-cPn H H HH 5-1764 H H Et 2 —(CH₂)₅-cHx H H H H 5-1765 H H Et 2 —(CH₂)₅-cHx Me H HH 5-1766 H H Et 2 —(CH₂)₅-cHx H Me H H 5-1767 H H Et 2 —(CH₂)₅-cHx F H HH 5-1768 H H Et 2 —(CH₂)₅-cHx H F H H 5-1769 H Me Et 2 —(CH₂)₅-cHx H H HH 5-1770 CO₂Me H Et 2 —(CH₂)₅-cHx H H H H 5-1771 CO₂Et H Et 2—(CH₂)₅-cHx H H H H 5-1772 H H Et 2 —(CH₂)₅-(4-F-cHx) H H H H 5-1773 H HEt 2 —(CH₂)₅-(4-Cl-cHx) H H H H 5-1774 H H Et 2 —(CH₂)₅-(4-Br-cHx) H H HH 5-1775 H H Et 2 —(CH₂)₅-(4-Me-cHx) H H H H 5-1776 H H Et 2—(CH₂)₅-(4-Et-cHx) H H H H 5-1777 H H Et 2 —(CH₂)₅-(4-Pr-cHx) H H H H5-1778 H H Et 2 —(CH₂)₅-(4-iPr-cHx) H H H H 5-1779 H H Et 2—(CH₂)₅-(4-CF₃-cHx) H H H H 5-1780 H H Et 2 —(CH₂)₅-(4-MeO-cHx) H H H H5-1781 H H Et 2 —(CH₂)₅-(4-EtO-cHx) H H H H 5-1782 H H Et 2—(CH₂)₅-(4-PrO-cHx) H H H H 5-1783 H H Et 2 —(CH₂)₅-(4-iPrO-cHx) H H H H5-1784 H H Et 2 —(CH₂)₅-(3-MeS-cHx) H H H H 5-1785 H H Et 2—(CH₂)₅-(4-MeS-cHx) H H H H 5-1786 H H Et 2 —(CH₂)₅-(2,4-diMe-cHx) H H HH 5-1787 H H Et 2 —(CH₂)₅-(3,4-diMe-cHx) H H H H 5-1788 H H Et 2—(CH₂)₅-(3,5-diMe-cHx) H H H H 5-1789 H H Et 2 —(CH₂)₅-Ph H H H H 5-1790H H Et 2 —(CH₂)₅-Ph Me H H H 5-1791 H H Et 2 —(CH₂)₅-Ph H Me H H 5-1792H H Et 2 —(CH₂)₅-Ph F H H H 5-1793 H H Et 2 —(CH₂)₅-Ph H F H H 5-1794 HMe Et 2 —(CH₂)₅-Ph H H H H 5-1795 CO₂Me H Et 2 —(CH₂)₅-Ph H H H H 5-1796CO₂Et H Et 2 —(CH₂)₅-Ph H H H H 5-1797 H H Et 2 —(CH₂)₅-(4-F-Ph) H H H H5-1798 H H Et 2 —(CH₂)₅-(4-Cl-Ph) H H H H 5-1799 H H Et 2—(CH₂)₅-(4-Br-Ph) H H H H 5-1800 H H Et 2 —(CH₂)₅-(4-Me-Ph) H H H H5-1801 H H Et 2 —(CH₂)₅-(4-Et-Ph) H H H H 5-1802 H H Et 2—(CH₂)₅-(4-Pr-Ph) H H H H 5-1803 H H Et 2 —(CH₂)₅-(4-iPr-Ph) H H H H5-1804 H H Et 2 —(CH₂)₅-(4-Bu-Ph) H H H H 5-1805 H H Et 2—(CH₂)₅-(4-CF₃-Ph) H H H H 5-1806 H H Et 2 —(CH₂)₅-(4-MeO-Ph) H H H H5-1807 H H Et 2 —(CH₂)₅-(4-EtO-Ph) H H H H 5-1808 H H Et 2—(CH₂)₅-(4-PrO-Ph) H H H H 5-1809 H H Et 2 —(CH₂)₅-(4-iPrO-Ph) H H H H5-1810 H H Et 2 —(CH₂)₅-(3-MeS-Ph) H H H H 5-1811 H H Et 2—(CH₂)₅-(4-MeS-Ph) H H H H 5-1812 H H Et 2 —(CH₂)₅-(2,4-diMe-Ph) H H H H5-1813 H H Et 2 —(CH₂)₅-(3,4-diMe-Ph) H H H H 5-1814 H H Et 2—(CH₂)₅-(3,5-diMe-Ph) H H H H 5-1815 H H Et 2 —(CH₂)₆-cPn H H H H 5-1816H H Et 2 —(CH₂)₆-cHx H H H H 5-1817 H H Et 2 —(CH₂)₆-cHx Me H H H 5-1818H H Et 2 —(CH₂)₆-cHx H Me H H 5-1819 H H Et 2 —(CH₂)₆-cHx F H H H 5-1820H H Et 2 —(CH₂)₆-cHx H F H H 5-1821 H Me Et 2 —(CH₂)₆-cHx H H H H 5-1822CO₂Me H Et 2 —(CH₂)₆-cHx H H H H 5-1823 CO₂Et H Et 2 —(CH₂)₆-cHx H H H H5-1824 H H Et 2 —(CH₂)₆-(4-F-cHx) H H H H 5-1825 H H Et 2—(CH₂)₆-(4-Cl-cHx) H H H H 5-1826 H H Et 2 —(CH₂)₆-(4-Br-cHx) H H H H5-1827 H H Et 2 —(CH₂)₆-(4-Me-cHx) H H H H 5-1828 H H Et 2—(CH₂)₆-(4-Et-cHx) H H H H 5-1829 H H Et 2 —(CH₂)₆-(4-Pr-cHx) H H H H5-1830 H H Et 2 —(CH₂)₆-(4-iPr-cHx) H H H H 5-1831 H H Et 2—(CH₂)₆-(4-Bu-cHx) H H H H 5-1832 H H Et 2 —(CH₂)₆-(4-CF₃-cHx) H H H H5-1833 H H Et 2 —(CH₂)₆-(4-MeO-cHx) H H H H 5-1834 H H Et 2—(CH₂)₆-(4-EtO-cHx) H H H H 5-1835 H H Et 2 —(CH₂)₆-(4-PrO-cHx) H H H H5-1836 H H Et 2 —(CH₂)₆-(4-iPrO-cHx) H H H H 5-1837 H H Et 2—(CH₂)₆-(3-MeS-cHx) H H H H 5-1838 H H Et 2 —(CH₂)₆-(4-MeS-cHx) H H H H5-1839 H H Et 2 —(CH₂)₆-(2,4-diMe-cHx) H H H H 5-1840 H H Et 2—(CH₂)₆-(3,4-diMe-cHx) H H H H 5-1841 H H Et 2 —(CH₂)₆-(3,5-diMe-cHx) HH H H 5-1842 H H Et 2 —(CH₂)₆-Ph H H H H 5-1843 H H Et 2 —(CH₂)₆-Ph Me HH H 5-1844 H H Et 2 —(CH₂)₆-Ph H Me H H 5-1845 H H Et 2 —(CH₂)₆-Ph F H HH 5-1846 H H Et 2 —(CH₂)₆-Ph H F H H 5-1847 H Me Et 2 —(CH₂)₆-Ph H H H H5-1848 CO₂Me H Et 2 —(CH₂)₆-Ph H H H H 5-1849 CO₂Et H Et 2 —(CH₂)₆-Ph HH H H 5-1850 H H Et 2 —(CH₂)₆-(4-F-Ph) H H H H 5-1851 H H Et 2—(CH₂)₆-(4-Cl-Ph) H H H H 5-1852 H H Et 2 —(CH₂)₆-(4-Br-Ph) H H H H5-1853 H H Et 2 —(CH₂)₆-(4-Me-Ph) H H H H 5-1854 H H Et 2—(CH₂)₆-(4-Et-Ph) H H H H 5-1855 H H Et 2 —(CH₂)₆-(4-Pr-Ph) H H H H5-1856 H H Et 2 —(CH₂)₆-(4-iPr-Ph) H H H H 5-1857 H H Et 2—(CH₂)₆-(4-Bu-Ph) H H H H 5-1858 H H Et 2 —(CH₂)₆-(4-CF₃-Ph) H H H H5-1859 H H Et 2 —(CH₂)₆-(4-MeO-Ph) H H H H 5-1860 H H Et 2—(CH₂)₆-(4-EtO-Ph) H H H H 5-1861 H H Et 2 —(CH₂)₆-(4-PrO-Ph) H H H H5-1862 H H Et 2 —(CH₂)₆-(4-iPrO-Ph) H H H H 5-1863 H H Et 2—(CH₂)₆-(3-MeS-Ph) H H H H 5-1864 H H Et 2 —(CH₂)₆-(4-MeS-Ph) H H H H5-1865 H H Et 2 —(CH₂)₆-(2,4-diMe-Ph) H H H H 5-1866 H H Et 2—(CH₂)₆-(3,4-diMe-Ph) H H H H 5-1867 H H Et 2 —(CH₂)₆-(3,5-diMe-Ph) H HH H 5-1868 H H Et 2 —(CH₂)₇-cHx H H H H 5-1869 H H Et 2 —(CH₂)₇-Ph H H HH 5-1870 H H Et 2 —CH═CH-cHx H H H H 5-1871 H H Et 2 —CH═CH-Ph H H H H5-1872 H H Et 2 —CH═CH—(CH₂)₃-cHx H H H H 5-1873 H Me Et 2—CH═CH—(CH₂)₃-cHx H H H H 5-1874 CO₂Me H Et 2 —CH═CH—(CH₂)₃-cHx H H H H5-1875 CO₂Et H Et 2 —CH═CH—(CH₂)₃-cHx H H H H 5-1876 H H Et 2—CH═CH—(CH₂)₃-Ph H H H H 5-1877 H Me Et 2 —CH═CH—(CH₂)₃-Ph H H H H5-1878 CO₂Me H Et 2 —CH═CH—(CH₂)₃-Ph H H H H 5-1879 CO₂Et H Et 2—CH═CH—(CH₂)₃-Ph H H H H 5-1880 H H Et 2 —CH═CH—(CH₂)₄-cHx H H H H5-1881 H Me Et 2 —CH═CH—(CH₂)₄-cHx H H H H 5-1882 CO₂Me H Et 2—CH═CH—(CH₂)₄-cHx H H H H 5-1883 CO₂Et H Et 2 —CH═CH—(CH₂)₄-cHx H H H H5-1884 H H Et 2 —CH═CH—(CH₂)₄-Ph H H H H 5-1885 H Me Et 2—CH═CH—(CH₂)₄-Ph H H H H 5-1886 CO₂Me H Et 2 —CH═CH—(CH₂)₄-Ph H H H H5-1887 CO₂Et H Et 2 —CH═CH—(CH₂)₄-Ph H H H H 5-1888 H H Et 2—CH═CH—CH₂O-cHx H H H H 5-1889 H H Et 2 —CH═CH—CH₂O-Ph H H H H 5-1890 HH Et 2 —CH═CH—(CH₂)₂O-cHx H H H H 5-1891 H H Et 2 —CH═CH—(CH₂)₂O-Ph H HH H 5-1892 H H Et 2 —C≡C—CH₂-cHx H H H H 5-1893 H Me Et 2 —C≡C—CH₂-cHx HH H H 5-1894 CO₂Me H Et 2 —C≡C—CH₂-cHx H H H H 5-1895 CO₂Et H Et 2—C≡C—CH₂-cHx H H H H 5-1896 H H Et 2 —C≡C—CH₂-Ph H H H H 5-1897 H Me Et2 —C≡C—CH₂-Ph H H H H 5-1898 CO₂Me H Et 2 —C≡C—CH₂-Ph H H H H 5-1899CO₂Et H Et 2 —C≡C—CH₂-Ph H H H H 5-1900 H H Et 2 —C≡C—(CH₂)₂-cHx H H H H5-1901 H Me Et 2 —C≡C—(CH₂)₂-cHx H H H H 5-1902 CO₂Me H Et 2—C≡C—(CH₂)₂-cHx H H H H 5-1903 CO₂Et H Et 2 —C≡C—(CH₂)₂-cHx H H H H5-1904 H H Et 2 —C≡C—(CH₂)₂-Ph H H H H 5-1905 H Me Et 2 —C≡C—(CH₂)₂-Ph HH H H 5-1906 CO₂Me H Et 2 —C≡C—(CH₂)₂-Ph H H H H 5-1907 CO₂Et H Et 2—C≡C—(CH₂)₂-Ph H H H H 5-1908 H H Et 2 —C═C—(CH₂)₃-cPn H H H H 5-1909 HH Et 2 —C≡C—(CH₂)₃-cHx H H H H 5-1910 H H Et 2 —C≡C—(CH₂)₃-cHx Me H H H5-1911 H H Et 2 —C≡C—(CH₂)₃-cHx H Me H H 5-1912 H H Et 2 —C≡C—(CH₂)₃-cHxF H H H 5-1913 H H Et 2 —C≡C—(CH₂)₃-cHx H F H H 5-1914 H Me Et 2—C≡C—(CH₂)₃-cHx H H H H 5-1915 CO₂Me H Et 2 —C≡C—(CH₂)₃-cHx H H H H5-1916 CO₂Et H Et 2 —C≡C—(CH₂)₃-cHx H H H H 5-1917 H H Et 2—C≡C—(CH₂)₃-(4-F-cHx) H H H H 5-1918 H H Et 2 —C≡C—(CH₂)₃-(4-Cl-cHx) H HH H 5-1919 H H Et 2 —C≡C—(CH₂)₃-(4-Br-cHx) H H H H 5-1920 H H Et 2—C≡C—(CH₂)₃-(4-Me-cHx) H H H H 5-1921 H H Et 2 —C≡C—(CH₂)₃-(4-Et-cHx) HH H H 5-1922 H H Et 2 —C≡C—(CH₂)₃-(4-Pr-cHx) H H H H 5-1923 H H Et 2—C≡C—(CH₂)₃-(4-iPr-cHx) H H H H 5-1924 H H Et 2 —C≡C—(CH₂)₃-(4-Bu-cHx) HH H H 5-1925 H H Et 2 —C≡C—(CH₂)₃-(4-CF₃-cHx) H H H H 5-1926 H H Et 2—C≡C—(CH₂)₃-(4-MeO-cHx) H H H H 5-1927 H H Et 2 —C≡C—(CH₂)₃-(4-EtO-cHx)H H H H 5-1928 H H Et 2 —C≡C—(CH₂)₃-(4-PrO-cHx) H H H H 5-1929 H H Et 2—C≡C—(CH₂)₃-(4-iPrO-cHx) H H H H 5-1930 H H Et 2 —C≡C—(CH₂)₃-(3-MeS-cHx)H H H H 5-1931 H H Et 2 —C≡C—(CH₂)₃-(4-MeS-cHx) H H H H 5-1932 H H Et 2—C≡C—(CH₂)₃-(2,4-diMe-cHx) H H H H 5-1933 H H Et 2—C≡C—(CH₂)₃-(3,4-diMe-cHx) H H H H 5-1934 H H Et 2—C≡C—(CH₂)₃-(3,5-diMe-cHx) H H H H 5-1935 H H Et 2 —C≡C—(CH₂)₃-Ph H H HH 5-1936 H H Et 2 —C≡C—(CH₂)₃-Ph Me H H H 5-1937 H H Et 2 —C≡C—(CH₂)₃-PhH Me H H 5-1938 H H Et 2 —C≡C—(CH₂)₃-Ph F H H H 5-1939 H H Et 2—C≡C—(CH₂)₃-Ph H F H H 5-1940 H Me Et 2 —C≡C—(CH₂)₃-Ph H H H H 5-1941CO₂Me H Et 2 —C≡C—(CH₂)₃-Ph H H H H 5-1942 CO₂Et H Et 2 —C≡C—(CH₂)₃-Ph HH H H 5-1943 H H Et 2 —C≡C—(CH₂)₃-(4-F-Ph) H H H H 5-1944 H H Et 2—C≡C—(CH₂)₃-(4-Cl-Ph) H H H H 5-1945 H H Et 2 —C≡C—(CH₂)₃-(4-Br-Ph) H HH H 5-1946 H H Et 2 —C≡C—(CH₂)₃-(4-Me-Ph) H H H H 5-1947 H H Et 2—C≡C—(CH₂)₃-(4-Et-Ph) H H H H 5-1948 H H Et 2 —C≡C—(CH₂)₃-(4-Pr-Ph) H HH H 5-1949 H H Et 2 —C≡C—(CH₂)₃-(4-iPr-Ph) H H H H 5-1950 H H Et 2—C≡C—(CH₂)₃-(4-Bu-Ph) H H H H 5-1951 H H Et 2 —C≡C—(CH₂)₃-(4-CF₃-Ph) H HH H 5-1952 H H Et 2 —C≡C—(CH₂)₃-(4-MeO-Ph) H H H H 5-1953 H H Et 2—C≡C—(CH₂)₃-(4-EtO-Ph) H H H H 5-1954 H H Et 2 —C≡C—(CH₂)₃-(4-PrO-Ph) HH H H 5-1955 H H Et 2 —C≡C—(CH₂)₃-(4-iPrO-Ph) H H H H 5-1956 H H Et 2—C≡C—(CH₂)₃-(3-MeS-Ph) H H H H 5-1957 H H Et 2 —C≡C—(CH₂)₃-(4-MeS-Ph) HH H H 5-1958 H H Et 2 —C≡C—(CH₂)₃-(2,4-diMe-Ph) H H H H 5-1959 H H Et 2—C≡C—(CH₂)₃-(3,4-diMe-Ph) H H H H 5-1960 H H Et 2—C≡C—(CH₂)₃-(3,5-diMe-Ph) H H H H 5-1961 H H Et 2 —C≡C—(CH₂)₄-cPn H H HH 5-1962 H H Et 2 —C≡C—(CH₂)₄-cHx H H H H 5-1963 H H Et 2—C≡C—(CH₂)₄-cHx Me H H H 5-1964 H H Et 2 —C≡C—(CH₂)₄-cHx H Me H H 5-1965H H Et 2 —C≡C—(CH₂)₄-cHx F H H H 5-1966 H H Et 2 —C≡C—(CH₂)₄-cHx H F H H5-1967 H Me Et 2 —C≡C—(CH₂)₄-cHx H H H H 5-1968 CO₂Me H Et 2—C≡C—(CH₂)₄-cHx H H H H 5-1969 CO₂Et H Et 2 —C≡C—(CH₂)₄-cHx H H H H5-1970 H H Et 2 —C≡C—(CH₂)₄-(4-F-cHx) H H H H 5-1971 H H Et 2—C≡C—(CH₂)₄-(4-Cl-cHx) H H H H 5-1972 H H Et 2 —C≡C—(CH₂)₄-(4-Br-cHx) HH H H 5-1973 H H Et 2 —C≡C—(CH₂)₄-(4-Me-cHx) H H H H 5-1974 H H Et 2—C≡C—(CH₂)₄-(4-Et-cHx) H H H H 5-1975 H H Et 2 —C≡C—(CH₂)₄-(4-Pr-cHx) HH H H 5-1976 H H Et 2 —C≡C—(CH₂)₄-(4-iPr-cHx) H H H H 5-1977 H H Et 2—C≡C—(CH₂)₄-(4-Bu-cHx) H H H H 5-1978 H H Et 2 —C≡C—(CH₂)₄-(4-CF₃-cHx) HH H H 5-1979 H H Et 2 —C≡C—(CH₂)₄-(4-MeO-cHx) H H H H 5-1980 H H Et 2—C≡C—(CH₂)₄-(4-EtO-cHx) H H H H 5-1981 H H Et 2 —C≡C—(CH₂)₄-(4-PrO-cHx)H H H H 5-1982 H H Et 2 —C≡C—(CH₂)₄-(4-iPrO-cHx) H H H H 5-1983 H H Et 2—C≡C—(CH₂)₄-(4-MeS-cHx) H H H H 5-1984 H H Et 2—C≡C—(CH₂)₄-(2,4-diMe-cHx) H H H H 5-1985 H H Et 2—C≡C—(CH₂)₄-(3,4-diMe-cHx) H H H H 5-1986 H H Et 2—C≡C—(CH₂)₄-(3,5-diMe-cHx) H H H H 5-1987 H H Et 2 —C≡C—(CH₂)₄-Ph H H HH 5-1988 H H Et 2 —C≡C—(CH₂)₄-Ph Me H H H 5-1989 H H Et 2 —C≡C—(CH₂)₄-PhH Me H H 5-1990 H H Et 2 —C≡C—(CH₂)₄-Ph F H H H 5-1991 H H Et 2—C≡C—(CH₂)₄-Ph H F H H 5-1992 H Me Et 2 —C≡C—(CH₂)₄-Ph H H H H 5-1993CO₂Me H Et 2 —C≡C—(CH₂)₄-Ph H H H H 5-1994 CO₂Et H Et 2 —C≡C—(CH₂)₄-Ph HH H H 5-1995 H H Et 2 —C≡C—(CH₂)₄-(4-F-Ph) H H H H 5-1996 H H Et 2—C≡C—(CH₂)₄-(4-Cl-Ph) H H H H 5-1997 H H Et 2 —C≡C—(CH₂)₄-(4-Br-Ph) H HH H 5-1998 H H Et 2 —C≡C—(CH₂)₄-(4-Me-Ph) H H H H 5-1999 H H Et 2—C≡C—(CH₂)₄-(4-Et-Ph) H H H H 5-2000 H H Et 2 —C≡C—(CH₂)₄-(4-Pr-Ph) H HH H 5-2001 H H Et 2 —C≡C—(CH₂)₄-(4-iPr-Ph) H H H H 5-2002 H H Et 2—C≡C—(CH₂)₄-(4-Bu-Ph) H H H H 5-2003 H H Et 2 —C≡C—(CH₂)₄-(4-CF₃-Ph) H HH H 5-2004 H H Et 2 —C≡C—(CH₂)₄-(4-MeO-Ph) H H H H 5-2005 H H Et 2—C≡C—(CH₂)₄-(4-EtO-Ph) H H H H 5-2006 H H Et 2 —C≡C—(CH₂)₄-(4-PrO-Ph) HH H H 5-2007 H H Et 2 —C≡C—(CH₂)₄-(4-iPrO-Ph) H H H H 5-2008 H H Et 2—C≡C—(CH₂)₄-(3-MeS-Ph) H H H H 5-2009 H H Et 2 —C≡C—(CH₂)₄-(4-MeS-Ph) HH H H 5-2010 H H Et 2 —C≡C—(CH₂)₄-(2,4-diMe-Ph) H H H H 5-2011 H H Et 2—C≡C—(CH₂)₄-(3,4-diMe-Ph) H H H H 5-2012 H H Et 2—C≡C—(CH₂)₄-(3,5-diMe-Ph) H H H H 5-2013 H H Et 2 —C≡C—(CH₂)₅-cHx H H HH 5-2014 H Me Et 2 —C≡C—(CH₂)₅-cHx H H H H 5-2015 CO₂Me H Et 2—C≡C—(CH₂)₅-cHx H H H H 5-2016 CO₂Et H Et 2 —C≡C—(CH₂)₅-cHx H H H H5-2017 H H Et 2 —C≡C—(CH₂)₅-Ph H H H H 5-2018 H Me Et 2 —C≡C—(CH₂)₅-Ph HH H H 5-2019 CO₂Me H Et 2 —C≡C—(CH₂)₅-Ph H H H H 5-2020 CO₂Et H Et 2—C≡C—(CH₂)₅-Ph H H H H 5-2021 H H Et 2 —C≡C—(CH₂)₆-cHx H H H H 5-2022 HMe Et 2 —C≡C—(CH₂)₆-cHx H H H H 5-2023 CO₂Me H Et 2 —C≡C—(CH₂)₆-cHx H HH H 5-2024 CO₂Et H Et 2 —C≡C—(CH₂)₆-cHx H H H H 5-2025 H H Et 2—C≡C—(CH₂)₆-Ph H H H H 5-2026 H Me Et 2 —C≡C—(CH₂)₆-Ph H H H H 5-2027CO₂Me H Et 2 —C≡C—(CH₂)₆-Ph H H H H 5-2028 CO₂Et H Et 2 —C≡C—(CH₂)₆-Ph HH H H 5-2029 H H Et 2 —C≡C—CH₂O-cHx H H H H 5-2030 H Me Et 2—C≡C—CH₂O-cHx H H H H 5-2031 CO₂Me H Et 2 —C≡C—CH₂O-cHx H H H H 5-2032CO₂Et H Et 2 —C≡C—CH₂O-cHx H H H H 5-2033 H H Et 2 —C≡C—CH₂O-Ph H H H H5-2034 H Me Et 2 —C≡C—CH₂O-Ph H H H H 5-2035 CO₂Me H Et 2 —C≡C—CH₂O-Ph HH H H 5-2036 CO₂Et H Et 2 —C≡C—CH₂O-Ph H H H H 5-2037 H H Et 2—C≡C—(CH₂)₂O-cPn H H H H 5-2038 H H Et 2 —C≡C—(CH₂)₂O-cHx H H H H 5-2039H H Et 2 —C≡C—(CH₂)₂O-cHx Me H H H 5-2040 H H Et 2 —C≡C—(CH₂)₂O-cHx H MeH H 5-2041 H H Et 2 —C≡C—(CH₂)₂O-cHx F H H H 5-2042 H H Et 2—C≡C—(CH₂)₂O-cHx H F H H 5-2043 H Me Et 2 —C≡C—(CH₂)₂O-cHx H H H H5-2044 CO₂Me H Et 2 —C≡C—(CH₂)₂O-cHx H H H H 5-2045 CO₂Et H Et 2—C≡C—(CH₂)₂O-cHx H H H H 5-2046 H H Et 2 —C≡C—(CH₂)₂O-(4-F-cHx) H H H H5-2047 H H Et 2 —C≡C—(CH₂)₂O-(4-Cl-cHx) H H H H 5-2048 H H Et 2—C≡C—(CH₂)₂O-(4-Br-cHx) H H H H 5-2049 H H Et 2 —C≡C—(CH₂)₂O-(4-Me-cHx)H H H H 5-2050 H H Et 2 —C≡C—(CH₂)₂O-(4-Et-cHx) H H H H 5-2051 H H Et 2—C≡C—(CH₂)₂O-(4-Pr-cHx) H H H H 5-2052 H H Et 2 —C≡C—(CH₂)₂O-(4-iPr-cHx)H H H H 5-2053 H H Et 2 —C≡C—(CH₂)₂O-(4-Bu-cHx) H H H H 5-2054 H H Et 2—C≡C—(CH₂)₂O-(4-CF₃-cHx) H H H H 5-2055 H H Et 2—C≡C—(CH₂)₂O-(4-MeO-cHx) H H H H 5-2056 H H Et 2—C≡C—(CH₂)₂O-(4-EtO-cHx) H H H H 5-2057 H H Et 2—C≡C—(CH₂)₂O-(4-PrO-cHx) H H H H 5-2058 H H Et 2—C≡C—(CH₂)₂O-(4-iPrO-cHx) H H H H 5-2059 H H Et 2—C≡C—(CH₂)₂O-(3-MeS-cHx) H H H H 5-2060 H H Et 2—C≡C—(CH₂)₂O-(4-MeS-cHx) H H H H 5-2061 H H Et 2—C≡C—(CH₂)₂O-(2,4-diMe-cHx) H H H H 5-2062 H H Et 2—C≡C—(CH₂)₂O-(3,4-diMe-cHx) H H H H 5-2063 H H Et 2—C≡C—(CH₂)₂O-(3,5-diMe-cHx) H H H H 5-2064 H H Et 2 —C≡C—(CH₂)₂O-Ph H HH H 5-2065 H H Et 2 —C≡C—(CH₂)₂O-Ph Me H H H 5-2066 H H Et 2—C≡C—(CH₂)₂O-Ph H Me H H 5-2067 H H Et 2 —C≡C—(CH₂)₂O-Ph F H H H 5-2068H H Et 2 —C≡C—(CH₂)₂O-Ph H F H H 5-2069 H Me Et 2 —C≡C—(CH₂)₂—OCH₂-Ph HH H H 5-2070 CO₂Me H Et 2 —C≡C—(CH₂)₂O-Ph H H H H 5-2071 CO₂Et H Et 2—C≡C—(CH₂)₂O-Ph H H H H 5-2072 H H Et 2 —C≡C—(CH₂)₂O-(4-F-Ph) H H H H5-2073 H H Et 2 —C≡C—(CH₂)₂O-(4-Cl-Ph) H H H H 5-2074 H H Et 2—C≡C—(CH₂)₂O-(4-Br-Ph) H H H H 5-2075 H H Et 2 —C≡C—(CH₂)₂O-(4-Me-Ph) HH H H 5-2076 H H Et 2 —C≡C—(CH₂)₂O-(4-Et-Ph) H H H H 5-2077 H H Et 2—C≡C—(CH₂)₂O-(4-Pr-Ph) H H H H 5-2078 H H Et 2 —C≡C—(CH₂)₂O-(4-iPr-Ph) HH H H 5-2079 H H Et 2 —C≡C—(CH₂)₂O-(4-Bu-Ph) H H H H 5-2080 H H Et 2—C≡C—(CH₂)₂O-(4-CF₃-Ph) H H H H 5-2081 H H Et 2 —C≡C—(CH₂)₂O-(4-MeO-Ph)H H H H 5-2082 H H Et 2 —C≡C—(CH₂)₂O-(4-EtO-Ph) H H H H 5-2083 H H Et 2—C≡C—(CH₂)₂O-(4-PrO-Ph) H H H H 5-2084 H H Et 2 —C≡C—(CH₂)₂O-(4-iPrO-Ph)H H H H 5-2085 H H Et 2 —C≡C—(CH₂)₂O-(4-MeS-Ph) H H H H 5-2086 H H Et 2—C≡C—(CH₂)₂O-(2,4-diMe-Ph) H H H H 5-2087 H H Et 2—C≡C—(CH₂)₂O-(3,4-diMe-Ph) H H H H 5-2088 H H Et 2—C≡C—(CH₂)₂O-(3,5-diMe-Ph) H H H H 5-2089 H H Et 2 —CO—(CH₂)₃-cHx H H HH 5-2090 H Me Et 2 —CO—(CH₂)₃-cHx H H H H 5-2091 CO₂Me H Et 2—CO—(CH₂)₃-cHx H H H H 5-2092 CO₂Et H Et 2 —CO—(CH₂)₃-cHx H H H H 5-2093H H Et 2 —CO—(CH₂)₃-Ph H H H H 5-2094 H Me Et 2 —CO—(CH₂)₃-Ph H H H H5-2095 CO₂Me H Et 2 —CO—(CH₂)₃-Ph H H H H 5-2096 CO₂Et H Et 2—CO—(CH₂)₃-Ph H H H H 5-2097 H H Et 2 —CO—(CH₂)₄-cHx H H H H 5-2098 H MeEt 2 —CO—(CH₂)₄-cHx H H H H 5-2099 CO₂Me H Et 2 —CO—(CH₂)₄-cHx H H H H5-2100 CO₂Et H Et 2 —CO—(CH₂)₄-cHx H H H H 5-2101 H H Et 2 —CO—(CH₂)₄-PhH H H H 5-2102 H Me Et 2 —CO—(CH₂)₄-Ph H H H H 5-2103 CO₂Me H Et 2—CO—(CH₂)₄-Ph H H H H 5-2104 CO₂Et H Et 2 —CO—(CH₂)₄-Ph H H H H 5-2105 HH Et 2 —CO—(CH₂)₅-cHx H H H H 5-2106 H Me Et 2 —CO—(CH₂)₅-cHx H H H H5-2107 CO₂Me H Et 2 —CO—(CH₂)₅-cHx H H H H 5-2108 CO₂Et H Et 2—CO—(CH₂)₅-cHx H H H H 5-2109 H H Et 2 —CO—(CH₂)₅-Ph H H H H 5-2110 H MeEt 2 —CO—(CH₂)₅-Ph H H H H 5-2111 CO₂Me H Et 2 —CO—(CH₂)₅-Ph H H H H5-2112 CO₂Et H Et 2 —CO—(CH₂)₅-Ph H H H H 5-2113 H H Et 2—CH(OH)—(CH₂)₄-cHx H H H H 5-2114 H Me Et 2 —CH(OH)—(CH₂)₄-cHx H H H H5-2115 CO₂Me H Et 2 —CH(OH)—(CH₂)₄-cHx H H H H 5-2116 CO₂Et H Et 2—CH(OH)—(CH₂)₄-cHx H H H H 5-2117 H H Et 2 —CH(OH)—(CH₂)₄-Ph H H H H5-2118 H Me Et 2 —CH(OH)—(CH₂)₄-Ph H H H H 5-2119 CO₂Me H Et 2—CH(OH)—(CH₂)₄-Ph H H H H 5-2120 CO₂Et H Et 2 —CH(OH)—(CH₂)₄-Ph H H H H5-2121 H H Et 2 —CH(OH)—(CH₂)₅-cHx H H H H 5-2122 H Me Et 2—CH(OH)—(CH₂)₅-cHx H H H H 5-2123 CO₂Me H Et 2 —CH(OH)—(CH₂)₅-cHx H H HH 5-2124 CO₂Et H Et 2 —CH(OH)—(CH₂)₅-cHx H H H H 5-2125 H H Et 2—CH(OH)—(CH₂)₅-Ph H H H H 5-2126 H Me Et 2 —CH(OH)—(CH₂)₅-Ph H H H H5-2127 CO₂Me H Et 2 —CH(OH)—(CH₂)₅-Ph H H H H 5-2128 CO₂Et H Et 2—CH(OH)—(CH₂)₅-Ph H H H H 5-2129 H H Et 2 -4-(cHx-CH₂O)Ph H H H H 5-2130H Me Et 2 -4-(cHx-CH₂O)Ph H H H H 5-2131 CO₂Me H Et 2 -4-(cHx-CH₂O)Ph HH H H 5-2132 CO₂Et H Et 2 -4-(cHx-CH₂O)Ph H H H H 5-2133 H H Et 2-4-[cHx-(CH₂)₂O]Ph H H H H 5-2134 H H Et 2 -4-[cHx-(CH₂)₃O]Ph H H H H5-2135 H H Et 2 -(4-BzO-Ph) H H H H 5-2136 H Me Et 2 -(4-BzO-Ph) H H H H5-2137 CO₂Me H Et 2 -(4-BzO-Ph) H H H H 5-2138 CO₂Et H Et 2 -(4-BzO-Ph)H H H H 5-2139 H H Et 2 -(4-BzO-2-F-Ph) H H H H 5-2140 H H Et 2-(4-BzO-3-F-Ph) H H H H 5-2141 H H Et 2 -(4-BzO-2,3-diF-Ph) H H H H5-2142 H H Et 2 -(4-BzO-2-Cl-Ph) H H H H 5-2143 H H Et 2-(4-BzO-3-Cl-Ph) H H H H 5-2144 H H Et 2 -(4-BzO-2,3-diCl-Ph) H H H H5-2145 H H Et 2 -(4-BzO-2-Me-Ph) H H H H 5-2146 H H Et 2-(4-BzO-3-Me-Ph) H H H H 5-2147 H H Et 2 -(4-BzO-2,3-diMe-Ph) H H H H5-2148 H H Et 2 -4-[Ph-(CH₂)₂O]-Ph H H H H 5-2149 H H Et 2-4-[Ph-(CH₂)₃O]-Ph H H H H 5-2150 H H Pr 2 —(CH₂)₅-cHx H H H H 5-2151 HH Pr 2 —(CH₂)₅-Ph H H H H 5-2152 H H Pr 2 —(CH₂)₆-cHx H H H H 5-2153 H HPr 2 —(CH₂)₆-Ph H H H H 5-2154 H H Pr 2 —C≡C—CH₂-cHx H H H H 5-2155 H HPr 2 —C≡C—(CH₂)₃-cHx H H H H 5-2156 H H Pr 2 —C≡C—(CH₂)₃-Ph H H H H5-2157 H H Pr 2 —C≡C—(CH₂)₄-cHx H H H H 5-2158 H H Pr 2 —C≡C—(CH₂)₄-Ph HH H H 5-2159 CO₂Me H Pr 2 —C≡C—CH₂O-Ph H H H H 5-2160 CO₂Et H Pr 2—C≡C—CH₂O-Ph H H H H 5-2161 H H Pr 2 —C≡C—(CH₂)₂O-cHx H H H H 5-2162 H HPr 2 —C≡C—(CH₂)₂O-Ph H H H H 5-2163 H H Pr 2 -4-(cHx-CH₂O)Ph H H H H5-2164 H H Pr 2 -(4-BzO-Ph) H H H H 5-2165 H H Me 3 —(CH₂)₅-cHx H H H H5-2166 H H Me 3 —(CH₂)₆-cHx H H H H 5-2167 H H Me 3 —CH═CH—(CH₂)₃-cHx HH H H 5-2168 H H Me 3 —CH═CH—(CH₂)₄-cHx H H H H 5-2169 H H Me 3—C≡C—(CH₂)₃-cHx H H H H 5-2170 H H Me 3 —C≡C—(CH₂)₄-cHx H H H H 5-2171 HH Me 3 —CO—(CH₂)₄-cHx H H H H 5-2172 H H Me 3 —CO—(CH₂)₅-cHx H H H H5-2173 H H Me 3 —CO—(CH₂)₄-Ph H H H H 5-2174 H H Me 3 —CO—(CH₂)₅-Ph H HH H 5-2175 H H Me 3 —CH(OH)—(CH₂)₄-cHx H H H H 5-2176 H H Me 3—CH(OH)—(CH₂)₅-cHx H H H H 5-2177 H H Me 3 -4-(cHx-CH₂O)Ph H H H H5-2178 H H Me 3 -(4-BzO-Ph) H H H H 5-2179 H H Me 3 —C≡C—CH₂O-cPn H H HH 5-2180 H H Me 3 —C≡C—(CH₂)₂O-cPn H H H H 5-2181 H H Me 3 —C≡C—CH₂O-cHxH H H H 5-2182 H H Me 3 —C≡C—(CH₂)₂O-cHx H H H H 5-2183 H H Me 3—C≡C—CH₂O-Ph H H H H 5-2184 H H Me 3 —C≡C—(CH₂)₂O-Ph H H H H 5-2185 H HMe 2 —(CH₂)₄-(3-F-Ph) H H H H 5-2186 H H Me 2 —(CH₂)₄-(3,4-diF-Ph) H H HH 5-2187 H H Me 2 —(CH₂)₄-(3,5-diF-Ph) H H H H 5-2188 H H Me 2—(CH₂)₄-(3-Cl-Ph) H H H H 5-2189 H H Me 2 —(CH₂)₄-(4-Cl-Ph) H H H H5-2190 H H Me 2 —(CH₂)₄-(3,4-diCl-Ph) H H H H 5-2191 H H Me 2—(CH₂)₄-(3,5-diCl-Ph) H H H H 5-2192 H H Me 2 —(CH₂)₄-(3-Me-Ph) H H H H5-2193 H H Me 2 —(CH₂)₄-(3,4-diMe-Ph) H H H H 5-2194 H H Me 2—(CH₂)₄-(3,5-diMe-Ph) H H H H 5-2195 H H Me 2 —(CH₂)₄-(3-CF₃-Ph) H H H H5-2196 H H Me 2 —(CH₂)₄-(3,4-diCF₃-Ph) H H H H 5-2197 H H Me 2—(CH₂)₄-(3,5-diCF₃-Ph) H H H H 5-2198 H H Me 2 —(CH₂)₄-(3-MeO-Ph) H H HH 5-2199 H H Me 2 —(CH₂)₄-(3,4-diMeO-Ph) H H H H 5-2200 H H Me 2—(CH₂)₄-(3,5-diMeO-Ph) H H H H 5-2201 H H Me 2 —(CH₂)₄-(3,4,5-triMeO-Ph)H H H H 5-2202 H H Me 2 —(CH₂)₄-(3-Ac-Ph) H H H H 5-2203 H H Me 2—(CH₂)₄-(4-Ac-Ph) H H H H 5-2204 H H Me 2 —(CH₂)₅-(3,4-diF-Ph) H H H H5-2205 H H Me 2 —(CH₂)₅-(3,5-diF-Ph) H H H H 5-2206 H H Me 2—(CH₂)₅-(3-Cl-Ph) H H H H 5-2207 H H Me 2 —(CH₂)₅-(3,4-diCl-Ph) H H H H5-2208 H H Me 2 —(CH₂)₅-(3,5-diCl-Ph) H H H H 5-2209 H H Me 2—(CH₂)₅-(3,4-diCF₃-Ph) H H H H 5-2210 H H Me 2 —(CH₂)₅-(3,5-diCF₃-Ph) HH H H 5-2211 H H Me 2 —(CH₂)₅-(3,4-diMeO-Ph) H H H H 5-2212 H H Me 2—(CH₂)₅-(3,5-diMeO-Ph) H H H H 5-2213 H H Me 2 —(CH₂)₅-(3,4,5-triMeO-Ph)H H H H 5-2214 H H Me 2 —(CH₂)₅-(3-Ac-Ph) H H H H 5-2215 H H Me 2—(CH₂)₅-(4-Ac-Ph) H H H H 5-2216 H H Me 2 —(CH₂)₃—O-(3-F-Ph) H H H H5-2217 H H Me 2 —(CH₂)₃—O-(3,4-diF-Ph) H H H H 5-2218 H H Me 2—(CH₂)₃—O-(3,5-diF-Ph) H H H H 5-2219 H H Me 2 —(CH₂)₃—O-(3-Me-Ph) H H HH 5-2220 H H Me 2 —(CH₂)₃—O-(3,4-diMe-Ph) H H H H 5-2221 H H Me 2—(CH₂)₃—O-(3,5-diMe-Ph) H H H H 5-2222 H H Me 2 —(CH₂)₃—O-(3-CF₃-Ph) H HH H 5-2223 H H Me 2 —(CH₂)₃—O-(3,4-diCF₃-Ph) H H H H 5-2224 H H Me 2—(CH₂)₃—O-(3,5-diCF₃-Ph) H H H H 5-2225 H H Me 2 —(CH₂)₃—O-(3-MeO-Ph) HH H H 5-2226 H H Me 2 —(CH₂)₃—O-(3,4-diMeO-Ph) H H H H 5-2227 H H Me 2—(CH₂)₃—O-(3,5-diMeO-Ph) H H H H 5-2228 H H Me 2—(CH₂)₃—O-(3,4,5-triMeO-Ph) H H H H 5-2229 H H Me 2 —(CH₂)₃—O-(3-Ac-Ph)H H H H 5-2230 H H Me 2 —(CH₂)₃—O-(4-Ac-Ph) H H H H 5-2231 H H Me 2—(CH₂)₄—O-(3,4-diF-Ph) H H H H 5-2232 H H Me 2 —(CH₂)₄—O-(3,5-diF-Ph) HH H H 5-2233 H H Me 2 —(CH₂)₄—O-(3,4-diMeO-Ph) H H H H 5-2234 H H Me 2—(CH₂)₄—O-(3,5-diMeO-Ph) H H H H 5-2235 H H Me 2—(CH₂)₄—O-(3,4,5-triMeO-Ph) H H H H 5-2236 H H Me 2 —(CH₂)₄—O-(3-Ac-Ph)H H H H 5-2237 H H Me 2 —(CH₂)₄—O-(4-Ac-Ph) H H H H 5-2238 H H Me 2—C≡C—(CH₂)₂-(3-F-Ph) H H H H 5-2239 H H Me 2 —C≡C—(CH₂)₂-(3,4-diF-Ph) HH H H 5-2240 H H Me 2 —C≡C—(CH₂)₂-(3,5-diF-Ph) H H H H 5-2241 H H Me 2—C≡C—(CH₂)₂-(3-Cl-Ph) H H H H 5-2242 H H Me 2 —C≡C—(CH₂)₂-(4-Cl-Ph) H HH H 5-2243 H H Me 2 —C≡C—(CH₂)₂-(3,4-diCl-Ph) H H H H 5-2244 H H Me 2—C≡C—(CH₂)₂-(3,5-diCl-Ph) H H H H 5-2245 H H Me 2 —C≡C—(CH₂)₂-(3-Me-Ph)H H H H 5-2246 H H Me 2 —C≡C—(CH₂)₂-(3,4-diMe-Ph) H H H H 5-2247 H H Me2 —C≡C—(CH₂)₂-(3,5-diMe-Ph) H H H H 5-2248 H H Me 2—C≡C—(CH₂)₂-(3-CF₃-Ph) H H H H 5-2249 H H Me 2—C≡C—(CH₂)₂-(3,4-diCF₃-Ph) H H H H 5-2250 H H Me 2—C≡C—(CH₂)₂-(3,5-diCF₃-Ph) H H H H 5-2251 H H Me 2—C≡C—(CH₂)₂-(3-MeO-Ph) H H H H 5-2252 H H Me 2—C≡C—(CH₂)₂-(3,4-diMeO-Ph) H H H H 5-2253 H H Me 2—C≡C—(CH₂)₂-(3,5-diMeO-Ph) H H H H 5-2254 H H Me 2—C≡C—(CH₂)₂-(3,4,5-triMeO-Ph) H H H H 5-2255 H H Me 2—C≡C—(CH₂)₂-(3-Ac-Ph) H H H H 5-2256 H H Me 2 —C≡C—(CH₂)₂-(4-Ac-Ph) H HH H 5-2257 H H Me 2 —C≡C—(CH₂)₃-(3,4-diF-Ph) H H H H 5-2258 H H Me 2—C≡C—(CH₂)₃-(3,5-diF-Ph) H H H H 5-2259 H H Me 2 —C≡C—(CH₂)₃-(3-Cl-Ph) HH H H 5-2260 H H Me 2 —C≡C—(CH₂)₃-(3,4-diCl-Ph) H H H H 5-2261 H H Me 2—C≡C—(CH₂)₃-(3,5-diCl-Ph) H H H H 5-2262 H H Me 2—C≡C—(CH₂)₃-(3,4-diCF₃-Ph) H H H H 5-2263 H H Me 2—C≡C—(CH₂)₃-(3,5-diCF₃-Ph) H H H H 5-2264 H H Me 2—C≡C—(CH₂)₃-(3,4-diMeO-Ph) H H H H 5-2265 H H Me 2—C≡C—(CH₂)₃-(3,5-diMeO-Ph) H H H H 5-2266 H H Me 2—C≡C—(CH₂)₃-(3,4,5-triMeO-Ph) H H H H 5-2267 H H Me 2—C≡C—(CH₂)₃-(3-Ac-Ph) H H H H 5-2268 H H Me 2 —C≡C—(CH₂)₃-(4-Ac-Ph) H HH H 5-2269 H H Me 2 —C≡C—CH₂—O-(3-F-Ph) H H H H 5-2270 H H Me 2—C≡C—CH₂—O-(3,4-diF-Ph) H H H H 5-2271 H H Me 2 —C≡C—CH₂—O-(3,5-diF-Ph)H H H H 5-2272 H H Me 2 —C≡C—CH₂—O-(3-Cl-Ph) H H H H 5-2273 H H Me 2—C≡C—CH₂—O-(4-Cl-Ph) H H H H 5-2274 H H Me 2 —C≡C—CH₂—O-(3,4-diCl-Ph) HH H H 5-2275 H H Me 2 —C≡C—CH₂—O-(3,5-diCl-Ph) H H H H 5-2276 H H Me 2—C≡C—CH₂—O-(3-Me-Ph) H H H H 5-2277 H H Me 2 —C≡C—CH₂—O-(2,4-diMe-Ph) HH H H 5-2278 H H Me 2 —C≡C—CH₂—O-(3,4-diMe-Ph) H H H H 5-2279 H H Me 2—C≡C—CH₂—O-(3,5-diMe-Ph) H H H H 5-2280 H H Me 2 —C≡C—CH₂—O-(3-CF₃-Ph) HH H H 5-2281 H H Me 2 —C≡C—CH₂—O-(3,4-diCF₃-Ph) H H H H 5-2282 H H Me 2—C≡C—CH₂—O-(3,5-diCF₃-Ph) H H H H 5-2283 H H Me 2 —C≡C—CH₂—O-(3-MeO-Ph)H H H H 5-2284 H H Me 2 —C≡C—CH₂—O-(3,4-diMeO-Ph) H H H H 5-2285 H H Me2 —C≡C—CH₂—O-(3,5-diMeO-Ph) H H H H 5-2286 H H Me 2—C≡C—CH₂—O-(3,4,5-triMeO-Ph) H H H H 5-2287 H H Me 2—C≡C—CH₂—O-(3-Ac-Ph) H H H H 5-2288 H H Me 2 —C≡C—CH₂—O-(4-Ac-Ph) H H HH 5-2289 H H Me 2 —C≡C—CH₂—O-(4-CO₂H-Ph) H H H H 5-2290 H H Me 2—C≡C—(CH₂)₂—O-(3,4-diF-Ph) H H H H 5-2291 H H Me 2—C≡C—(CH₂)₂—O-(3,5-diF-Ph) H H H H 5-2292 H H Me 2—C≡C—(CH₂)₂—O-(3-Cl-Ph) H H H H 5-2293 H H Me 2—C≡C—(CH₂)₂—O-(3,4-diCl-Ph) H H H H 5-2294 H H Me 2—C≡C—(CH₂)₂—O-(3,5-diCl-Ph) H H H H 5-2295 H H Me 2—C≡C—(CH₂)₂—O-(3,4-diCF₃-Ph) H H H H 5-2296 H H Me 2—C≡C—(CH₂)₂—O-(3,5-diCF₃-Ph) H H H H 5-2297 H H Me 2—C≡C—(CH₂)₂—O-(3,4-diMeO-Ph) H H H H 5-2298 H H Me 2—C≡C—(CH₂)₂—O-(3,5-diMeO-Ph) H H H H 5-2299 H H Me 2—C≡C—(CH₂)₂—O-(3,4,5-triMeO-Ph) H H H H 5-2300 H H Me 2—C≡C—(CH₂)₂—O-(3-Ac-Ph) H H H H 5-2301 H H Me 2 —C≡C—(CH₂)₂—O-(4-Ac-Ph)H H H H 5-2302 H H Me 2 —CO—(CH₂)₃-(3-F-Ph) H H H H 5-2303 H H Me 2—CO—(CH₂)₃-(4-F-Ph) H H H H 5-2304 H H Me 2 —CO—(CH₂)₃-(3,4-diF-Ph) H HH H 5-2305 H H Me 2 —CO—(CH₂)₃-(3,5-diF-Ph) H H H H 5-2306 H H Me 2—CO—(CH₂)₃-(3-Cl-Ph) H H H H 5-2307 H H Me 2 —CO—(CH₂)₃-(4-Cl-Ph) H H HH 5-2308 H H Me 2 —CO—(CH₂)₃-(3,4-diCl-Ph) H H H H 5-2309 H H Me 2—CO—(CH₂)₃-(3,5-diCl-Ph) H H H H 5-2310 H H Me 2 —CO—(CH₂)₃-(3-Me-Ph) HH H H 5-2311 H H Me 2 —CO—(CH₂)₃-(4-Me-Ph) H H H H 5-2312 H H Me 2—CO—(CH₂)₃-(3,4-diMe-Ph) H H H H 5-2313 H H Me 2—CO—(CH₂)₃-(3,5-diMe-Ph) H H H H 5-2314 H H Me 2 —CO—(CH₂)₃-(3-Et-Ph) HH H H 5-2315 H H Me 2 —CO—(CH₂)₃-(4-Et-Ph) H H H H 5-2316 H H Me 2—CO—(CH₂)₃-(3-CF₃-Ph) H H H H 5-2317 H H Me 2 —CO—(CH₂)₃-(4-CF₃-Ph) H HH H 5-2318 H H Me 2 —CO—(CH₂)₃-(3,4-diCF₃-Ph) H H H H 5-2319 H H Me 2—CO—(CH₂)₃-(3,5-diCF₃-Ph) H H H H 5-2320 H H Me 2 —CO—(CH₂)₃-(3-MeO-Ph)H H H H 5-2321 H H Me 2 —CO—(CH₂)₃-(4-MeO-Ph) H H H H 5-2322 H H Me 2—CO—(CH₂)₃-(3,4-diMeO-Ph) H H H H 5-2323 H H Me 2—CO—(CH₂)₃-(3,5-diMeO-Ph) H H H H 5-2324 H H Me 2—CO—(CH₂)₃-(3,4,5-triMeO-Ph) H H H H 5-2325 H H Me 2—CO—(CH₂)₃-(4-MeS-Ph) H H H H 5-2326 H H Me 2 —CO—(CH₂)₃-(3-Ac-Ph) H H HH 5-2327 H H Me 2 —CO—(CH₂)₃-(4-Ac-Ph) H H H H 5-2328 H H Me 2—CO—(CH₂)₄-(3-F-Ph) H H H H 5-2329 H H Me 2 —CO—(CH₂)₄-(3,4-diF-Ph) H HH H 5-2330 H H Me 2 —CO—(CH₂)₄-(3,5-diF-Ph) H H H H 5-2331 H H Me 2—CO—(CH₂)₄-(3-Cl-Ph) H H H H 5-2332 H H Me 2 —CO—(CH₂)₄-(4-Cl-Ph) H H HH 5-2333 H H Me 2 —CO—(CH₂)₄-(3,4-diCl-Ph) H H H H 5-2334 H H Me 2—CO—(CH₂)₄-(3,5-diCl-Ph) H H H H 5-2335 H H Me 2 —CO—(CH₂)₄-(3-Me-Ph) HH H H 5-2336 H H Me 2 —CO—(CH₂)₄-(3,4-diMe-Ph) H H H H 5-2337 H H Me 2—CO—(CH₂)₄-(3,5-diMe-Ph) H H H H 5-2338 H H Me 2 —CO—(CH₂)₄-(3-CF₃-Ph) HH H H 5-2339 H H Me 2 —CO—(CH₂)₄-(3,4-diCF₃-Ph) H H H H 5-2340 H H Me 2—CO—(CH₂)₄-(3,5-diCF₃-Ph) H H H H 5-2341 H H Me 2 —CO—(CH₂)₄-(3-MeO-Ph)H H H H 5-2342 H H Me 2 —CO—(CH₂)₄-(3,4-diMeO-Ph) H H H H 5-2343 H H Me2 —CO—(CH₂)₄-(3,5-diMeO-Ph) H H H H 5-2344 H H Me 2—CO—(CH₂)₄-(3,4,5-triMeO-Ph) H H H H 5-2345 H H Me 2—CO—(CH₂)₄-(3-Ac-Ph) H H H H 5-2346 H H Me 2 —CO—(CH₂)₄-(4-Ac-Ph) H H HH 5-2347 H H Me 2 —CH(OH)—(CH₂)₃-(3-F-Ph) H H H H 5-2348 H H Me 2—CH(OH)—(CH₂)₃-(4-F-Ph) H H H H 5-2349 H H Me 2—CH(OH)—(CH₂)₃-(3,4-diF-Ph) H H H H 5-2350 H H Me 2—CH(OH)—(CH₂)₃-(3,5-diF-Ph) H H H H 5-2351 H H Me 2—CH(OH)—(CH₂)₃-(3-Cl-Ph) H H H H 5-2352 H H Me 2—CH(OH)—(CH₂)₃-(4-Cl-Ph) H H H H 5-2353 H H Me 2—CH(OH)—(CH₂)₃-(3,4-diCl-Ph) H H H H 5-2354 H H Me 2—CH(OH)—(CH₂)₃-(3,5-diCl-Ph) H H H H 5-2355 H H Me 2—CH(OH)—(CH₂)₃-(3-Me-Ph) H H H H 5-2356 H H Me 2—CH(OH)—(CH₂)₃-(4-Me-Ph) H H H H 5-2357 H H Me 2—CH(OH)—(CH₂)₃-(3,4-diMe-Ph) H H H H 5-2358 H H Me 2—CH(OH)—(CH₂)₃-(3,5-diMe-Ph) H H H H 5-2359 H H Me 2—CH(OH)—(CH₂)₃-(3-Et-Ph) H H H H 5-2360 H H Me 2—CH(OH)—(CH₂)₃-(4-Et-Ph) H H H H 5-2361 H H Me 2—CH(OH)—(CH₂)₃-(3-CF₃-Ph) H H H H 5-2362 H H Me 2—CH(OH)—(CH₂)₃-(4-CF₃-Ph) H H H H 5-2363 H H Me 2—CH(OH)—(CH₂)₃-(3,4-diCF₃-Ph) H H H H 5-2364 H H Me 2—CH(OH)—(CH₂)₃-(3,5-diCF₃-Ph) H H H H 5-2365 H H Me 2—CH(OH)—(CH₂)₃-(3-MeO-Ph) H H H H 5-2366 H H Me 2—CH(OH)—(CH₂)₃-(4-MeO-Ph) H H H H 5-2367 H H Me 2—CH(OH)—(CH₂)₃-(3,4-diMeO-Ph) H H H H 5-2368 H H Me 2—CH(OH)—(CH₂)₃-(3,5-diMeO-Ph) H H H H 5-2369 H H Me 2—CH(OH)—(CH₂)₃-(3,4,5-triMeO-Ph) H H H H 5-2370 H H Me 2—CH(OH)—(CH₂)₃-(4-MeS-Ph) H H H H 5-2371 H H Me 2—CH(OH)—(CH₂)₃-(3-Ac-Ph) H H H H 5-2372 H H Me 2—CH(OH)—(CH₂)₃-(4-Ac-Ph) H H H H 5-2373 H H Me 2 —CH(OH)—(CH₂)₄-(3-F-Ph)H H H H 5-2374 H H Me 2 —CH(OH)—(CH₂)₄-(3,4-diF-Ph) H H H H 5-2375 H HMe 2 —CH(OH)—(CH₂)₄-(3,5-diF-Ph) H H H H 5-2376 H H Me 2—CH(OH)—(CH₂)₄-(3-Cl-Ph) H H H H 5-2377 H H Me 2—CH(OH)—(CH₂)₄-(4-Cl-Ph) H H H H 5-2378 H H Me 2—CH(OH)—(CH₂)₄-(3,4-diCl-Ph) H H H H 5-2379 H H Me 2—CH(OH)—(CH₂)₄-(3,5-diCl-Ph) H H H H 5-2380 H H Me 2—CH(OH)—(CH₂)₄-(3-Me-Ph) H H H H 5-2381 H H Me 2—CH(OH)—(CH₂)₄-(3,4-diMe-Ph) H H H H 5-2382 H H Me 2—CH(OH)—(CH₂)₄-(3,5-diMe-Ph) H H H H 5-2383 H H Me 2—CH(OH)—(CH₂)₄-(3-CF₃-Ph) H H H H 5-2384 H H Me 2—CH(OH)—(CH₂)₄-(3,4-diCF₃-Ph) H H H H 5-2385 H H Me 2—CH(OH)—(CH₂)₄-(3,5-diCF₃-Ph) H H H H 5-2386 H H Me 2—CH(OH)—(CH₂)₄-(3-MeO-Ph) H H H H 5-2387 H H Me 2—CH(OH)—(CH₂)₄-(3,4-diMeO-Ph) H H H H 5-2388 H H Me 2—CH(OH)—(CH₂)₄-(3,5-diMeO-Ph) H H H H 5-2389 H H Me 2—CH(OH)—(CH₂)₄-(3,4,5-triMeO-Ph) H H H H 5-2390 H H Me 2—CH(OH)—(CH₂)₄-(3-Ac-Ph) H H H H 5-2391 H H Me 2—CH(OH)—(CH₂)₄-(4-Ac-Ph) H H H H 5-2392 H H Me 2 —O—(CH₂)₃-cHx H H H H5-2393 H H Me 2 —O—(CH₂)₄-cHx H H H H 5-2394 H H Me 2 —O—(CH₂)₅-cHx H HH H 5-2395 H H Me 2 —O—(CH₂)₃-Ph H H H H 5-2396 H H Me 2 —O—(CH₂)₄-Ph HH H H 5-2397 H H Me 2 —O—(CH₂)₅-Ph H H H H 5-2398 COCH₃ H Me 2—(CH₂)₄-cHx H H H H 5-2399 COC₂H₅ H Me 2 —(CH₂)₄-cHx H H H H 5-2400COC₃H₇ H Me 2 —(CH₂)₄-cHx H H H H 5-2401 COC₄H₉ H Me 2 —(CH₂)₄-cHx H H HH 5-2402 COC₅H₁₁ H Me 2 —(CH₂)₄-cHx H H H H 5-2403 COC₆H₁₃ H Me 2—(CH₂)₄-cHx H H H H 5-2404 COC₇H₁₅ H Me 2 —(CH₂)₄-cHx H H H H 5-2405COC₈H₁₇ H Me 2 —(CH₂)₄-cHx H H H H 5-2406 COCH₃ H Me 2 —(CH₂)₄-Ph H H HH 5-2407 COC₂H₅ H Me 2 —(CH₂)₄-Ph H H H H 5-2408 COC₃H₇ H Me 2—(CH₂)₄-Fh H H H H 5-2409 COC₄H₉ H Me 2 —(CH₂)₄-Ph H H H H 5-2410COC₅H₁₁ H Me 2 —(CH₂)₄-Ph H H H H 5-2411 COC₆H₁₃ H Me 2 —(CH₂)₄-Ph H H HH 5-2412 COC₇H₁₅ H Me 2 —(CH₂)₄-Ph H H H H 5-2413 COC₈H₁₇ H Me 2—(CH₂)₄-Ph H H H H 5-2414 COCH₃ H Me 2 —(CH₂)₅-cHx H H H H 5-2415 COC₂H₅H Me 2 —(CH₂)₅-cHx H H H H 5-2416 COC₃H₇ H Me 2 —(CH₂)₅-cHx H H H H5-2417 COC₄H₉ H Me 2 —(CH₂)₅-cHx H H H H 5-2418 COC₅H₁₁ H Me 2—(CH₂)₅-cHx H H H H 5-2419 COC₆H₁₃ H Me 2 —(CH₂)₅-cHx H H H H 5-2420COC₇H₁₅ H Me 2 —(CH₂)₅-cHx H H H H 5-2421 COC₈H₁₇ H Me 2 —(CH₂)₅-cHx H HH H 5-2422 COCH₃ H Me 2 —(CH₂)₅-Ph H H H H 5-2423 COC₂H₅ H Me 2—(CH₂)₅-Ph H H H H 5-2424 COC₃H₇ H Me 2 —(CH₂)₅-Ph H H H H 5-2425 COC₄H₉H Me 2 —(CH₂)₅-Ph H H H H 5-2426 COC₅H₁₁ H Me 2 —(CH₂)₅-Ph H H H H5-2427 COC₆H₁₃ H Me 2 —(CH₂)₅-Ph H H H H 5-2428 COC₇H₁₅ H Me 2—(CH₂)₅-Ph H H H H 5-2429 COC₈H₁₇ H Me 2 —(CH₂)₅-Ph H H H H 5-2430 COCH₃H Me 2 —C≡C—(CH₂)₂-cHx H H H H 5-2431 COC₂H₅ H Me 2 —C≡C—(CH₂)₂-cHx H HH H 5-2432 COC₃H₇ H Me 2 —C≡C—(CH₂)₂-cHx H H H H 5-2433 COC₄H₉ H Me 2—C≡C—(CH₂)₂-cHx H H H H 5-2434 COC₅H₁₁ H Me 2 —C≡C—(CH₂)₂-cHx H H H H5-2435 COC₆H₁₃ H Me 2 —C≡C—(CH₂)₂-cHx H H H H 5-2436 COC₇H₁₅ H Me 2—C≡C—(CH₂)₂-cHx H H H H 5-2437 COC₈H₁₇ H Me 2 —C≡C—(CH₂)₂-cHx H H H H5-2438 COCH₃ H Me 2 —C≡C—(CH₂)₂-Ph H H H H 5-2439 COC₂H₅ H Me 2—C≡C—(CH₂)₂-Ph H H H H 5-2440 COC₃H₇ H Me 2 —C≡C—(CH₂)₂-Ph H H H H5-2441 COC₄H₉ H Me 2 —C≡C—(CH₂)₂-Ph H H H H 5-2442 COC₅H₁₁ H Me 2—C≡C—(CH₂)₂-Ph H H H H 5-2443 COC₆H₁₃ H Me 2 —C≡C—(CH₂)₂-Ph H H H H5-2444 COC₇H₁₅ H Me 2 —C≡C—(CH₂)₂-Ph H H H H 5-2445 COC₈H₁₇ H Me 2—C≡C—(CH₂)₂-Ph H H H H 5-2446 COCH₃ H Me 2 —C≡C—(CH₂)₃-cHx H H H H5-2447 COC₂H₅ H Me 2 —C≡C—(CH₂)₃-cHx H H H H 5-2448 COC₃H₇ H Me 2—C≡C—(CH₂)₃-cHx H H H H 5-2449 COC₄H₉ H Me 2 —C≡C—(CH₂)₃-cHx H H H H5-2450 COC₅H₁₁ H Me 2 —C≡C—(CH₂)₃-cHx H H H H 5-2451 COC₆H₁₃ H Me 2—C≡C—(CH₂)₃-cHx H H H H 5-2452 COC₇H₁₅ H Me 2 —C≡C—(CH₂)₃-cHx H H H H5-2453 COC₈H₁₇ H Me 2 —C≡C—(CH₂)₃-cHx H H H H 5-2454 COCH₃ H Me 2—C≡C—(CH₂)₃-Ph H H H H 5-2455 COC₂H₅ H Me 2 —C≡C—(CH₂)₃-Ph H H H H5-2456 COC₃H₇ H Me 2 —C≡C—(CH₂)₃-Ph H H H H 5-2457 COC₄H₉ H Me 2—C≡C—(CH₂)₃-Ph H H H H 5-2458 COC₅H₁₁ H Me 2 —C≡C—(CH₂)₃-Ph H H H H5-2459 COC₆H₁₃ H Me 2 —C≡C—(CH₂)₃-Ph H H H H 5-2460 COC₇H₁₅ H Me 2—C≡C—(CH₂)₃-Ph H H H H 5-2461 COC₈H₁₇ H Me 2 —C≡C—(CH₂)₃-Ph H H H H5-2462 COCH₃ H Me 2 —C≡C—(CH₂)₄-cHx H H H H 5-2463 COC₂H₅ H Me 2—C≡C—(CH₂)₄-cHx H H H H 5-2464 COC₃H₇ H Me 2 —C≡C—(CH₂)₄-cHx H H H H5-2465 COC₄H₉ H Me 2 —C≡C—(CH₂)₄-cHx H H H H 5-2466 COC₅H₁₁ H Me 2—C≡C—(CH₂)₄-cHx H H H H 5-2467 COC₆H₁₃ H Me 2 —C≡C—(CH₂)₄-cHx H H H H5-2468 COC₇H₁₅ H Me 2 —C≡C—(CH₂)₄-cHx H H H H 5-2469 COC₈H₁₇ H Me 2—C≡C—(CH₂)₄-cHx H H H H 5-2470 COCH₃ H Me 2 —C≡C—(CH₂)₄-Ph H H H H5-2471 COC₂H₅ H Me 2 —C≡C—(CH₂)₄-Ph H H H H 5-2472 COC₃H₇ H Me 2—C≡C—(CH₂)₄-Ph H H H H 5-2473 COC₄H₉ H Me 2 —C≡C—(CH₂)₄-Ph H H H H5-2474 COC₅H₁₁ H Me 2 —C≡C—(CH₂)₄-Ph H H H H 5-2475 COC₆H₁₃ H Me 2—C≡C—(CH₂)₄-Ph H H H H 5-2476 COC₇H₁₅ H Me 2 —C≡C—(CH₂)₄-Ph H H H H5-2477 COC₈H₁₇ H Me 2 —C≡C—(CH₂)₄-Ph H H H H 5-2478 COCH₃ H Me 2—C≡C—(CH₂)₂O-cHx H H H H 5-2479 COC₂H₅ H Me 2 —C≡C—(CH₂)₂O-cHx H H H H5-2480 COC₃H₇ H Me 2 —C≡C—(CH₂)₂O-cHx H H H H 5-2481 COC₄H₉ H Me 2—C≡C—(CH₂)₂O-cHx H H H H 5-2482 COC₅H₁₁ H Me 2 —C≡C—(CH₂)₂O-cHx H H H H5-2483 COC₆H₁₃ H Me 2 —C≡C—(CH₂)₂O-cHx H H H H 5-2484 COC₇H₁₅ H Me 2—C≡C—(CH₂)₂O-cHx H H H H 5-2485 COC₈H₁₇ H Me 2 —C≡C—(CH₂)₂O-cHx H H H H5-2486 COCH₃ H Me 2 —C≡C—(CH₂)₂O-Ph H H H H 5-2487 COC₂H₅ H Me 2—C≡C—(CH₂)₂O-Ph H H H H 5-2488 COC₃H₇ H Me 2 —C≡C—(CH₂)₂O-Ph H H H H5-2489 COC₄H₉ H Me 2 —C≡C—(CH₂)₂O-Ph H H H H 5-2490 COC₅H₁₁ H Me 2—C≡C—(CH₂)₂O-Ph H H H H 5-2491 COC₆H₁₃ H Me 2 —C≡C—(CH₂)₂O-Ph H H H H5-2492 COC₇H₁₅ H Me 2 —C≡C—(CH₂)₂O-Ph H H H H 5-2493 COC₈H₁₇ H Me 2—C≡C—(CH₂)₂O-Ph H H H H 5-2494 COCH₃ H Me 2 —CO—(CH₂)₃-cHx H H H H5-2495 COC₂H₅ H Me 2 —CO—(CH₂)₃-cHx H H H H 5-2496 COC₃H₇ H Me 2—CO—(CH₂)₃-cHx H H H H 5-2497 COC₄H₉ H Me 2 —CO—(CH₂)₃-cHx H H H H5-2498 COC₅H₁₁ H Me 2 —CO—(CH₂)₃-cHx H H H H 5-2499 COC₆H₁₃ H Me 2—CO—(CH₂)₃-cHx H H H H 5-2500 COC₇H₁₅ H Me 2 —CO—(CH₂)₃-cHx H H H H5-2501 COC₈H₁₇ H Me 2 —CO—(CH₂)₃-cHx H H H H 5-2502 COCH₃ H Me 2—CO—(CH₂)₃-Ph H H H H 5-2503 COC₂H₅ H Me 2 —CO—(CH₂)₃-Ph H H H H 5-2504COC₃H₇ H Me 2 —CO—(CH₂)₃-Ph H H H H 5-2505 COC₄H₉ H Me 2 —CO—(CH₂)₃-Ph HH H H 5-2506 COC₅H₁₁ H Me 2 —CO—(CH₂)₃-Ph H H H H 5-2507 COC₆H₁₃ H Me 2—CO—(CH₂)₃-Ph H H H H 5-2508 COC₇H₁₅ H Me 2 —CO—(CH₂)₃-Ph H H H H 5-2509COC₈H₁₇ H Me 2 —CO—(CH₂)₃-Ph H H H H 5-2510 COCH₃ H Me 2 —CO—(CH₂)₄-cHxH H H H 5-2511 COC₂H₅ H Me 2 —CO—(CH₂)₄-cHx H H H H 5-2512 COC₃H₇ H Me 2—CO—(CH₂)₄-cHx H H H H 5-2513 COC₄H₉ H Me 2 —CO—(CH₂)₄-cHx H H H H5-2514 COC₅H₁₁ H Me 2 —CO—(CH₂)₄-cHx H H H H 5-2515 COC₆H₁₃ H Me 2—CO—(CH₂)₄-cHx H H H H 5-2516 COC₇H₁₅ H Me 2 —CO—(CH₂)₄-cHx H H H H5-2517 COC₈H₁₇ H Me 2 —CO—(CH₂)₄-cHx H H H H 5-2518 COCH₃ H Me 2—CO—(CH₂)₄-Ph H H H H 5-2519 COC₂H₅ H Me 2 —CO—(CH₂)₄-Ph H H H H 5-2520COC₃H₇ H Me 2 —CO—(CH₂)₄-Ph H H H H 5-2521 COC₄H₉ H Me 2 —CO—(CH₂)₄-Ph HH H H 5-2522 COC₅H₁₁ H Me 2 —CO—(CH₂)₄-Ph H H H H 5-2523 COC₆H₁₃ H Me 2—CO—(CH₂)₄-Ph H H H H 5-2524 COC₇H₁₅ H Me 2 —CO—(CH₂)₄-Ph H H H H 5-2525COC₈H₁₇ H Me 2 —CO—(CH₂)₄-Ph H H H H 5-2526 COCH₃ H Me 2 —CO—(CH₂)₅-cHxH H H H 5-2527 COC₂H₅ H Me 2 —CO—(CH₂)₅-cHx H H H H 5-2528 COC₃H₇ H Me 2—CO—(CH₂)₅-cHx H H H H 5-2529 COC₄H₉ H Me 2 —CO—(CH₂)₅-cHx H H H H5-2530 COC₅H₁₁ H Me 2 —CO—(CH₂)₅-cHx H H H H 5-2531 COC₆H₁₃ H Me 2—CO—(CH₂)₅-cHx H H H H 5-2532 COC₇H₁₅ H Me 2 —CO—(CH₂)₅-cHx H H H H5-2533 COC₈H₁₇ H Me 2 —CO—(CH₂)₅-cHx H H H H 5-2534 COCH₃ H Me 2—CO—(CH₂)₅-Ph H H H H 5-2535 COC₂H₅ H Me 2 —CO—(CH₂)₅-Ph H H H H 5-2536COC₃H₇ H Me 2 —CO—(CH₂)₅-Ph H H H H 5-2537 COC₄H₉ H Me 2 —CO—(CH₂)₅-Ph HH H H 5-2538 COC₅H₁₁ H Me 2 —CO—(CH₂)₅-Ph H H H H 5-2539 COC₆H₁₃ H Me 2—CO—(CH₂)₅-Ph H H H H 5-2540 COC₇H₁₅ H Me 2 —CO—(CH₂)₅-Ph H H H H 5-2541COC₈H₁₇ H Me 2 —CO—(CH₂)₅-Ph H H H H 5-2542 COCH₃ H Me 2—CH(OH)—(CH₂)₄-cHx H H H H 5-2543 COC₂H₅ H Me 2 —CH(OH)—(CH₂)₄-cHx H H HH 5-2544 COC₃H₇ H Me 2 —CH(OH)—(CH₂)₄-cHx H H H H 5-2545 COC₄H₉ H Me 2—CH(OH)—(CH₂)₄-cHx H H H H 5-2546 COC₅H₁₁ H Me 2 —CH(OH)—(CH₂)₄-cHx H HH H 5-2547 COC₆H₁₃ H Me 2 —CH(OH)—(CH₂)₄-cHx H H H H 5-2548 COC₇H₁₅ H Me2 —CH(OH)—(CH₂)₄-cHx H H H H 5-2549 COC₈H₁₇ H Me 2 —CH(OH)—(CH₂)₄-cHx HH H H 5-2550 COCH₃ H Me 2 —CH(OH)—(CH₂)₄-Ph H H H H 5-2551 COC₂H₅ H Me 2—CH(OH)—(CH₂)₄-Ph H H H H 5-2552 COC₃H₇ H Me 2 —CH(OH)—(CH₂)₄-Ph H H H H5-2553 COC₄H₉ H Me 2 —CH(OH)—(CH₂)₄-Ph H H H H 5-2554 COC₅H₁₁ H Me 2—CH(OH)—(CH₂)₄-Ph H H H H 5-2555 COC₆H₁₃ H Me 2 —CH(OH)—(CH₂)₄-Ph H H HH 5-2556 COC₇H₁₅ H Me 2 —CH(OH)—(CH₂)₄-Ph H H H H 5-2557 COC₈H₁₇ H Me 2—CH(OH)—(CH₂)₄-Ph H H H H

TABLE 6

Compd. R¹ R² R⁴ n —Y—Z—R⁵ R⁶ R⁷ R¹⁰ R¹¹ 6-1 H H Me 1 —(CH₂)₅-cHx H H H H6-2 H H Me 1 —(CH₂)₆-cHx H H H H 6-3 H H Me 1 —C≡C—(CH₂)₃-cHx H H H H6-4 H H Me 1 —C≡C—(CH₂)₄-cHx H H H H 6-5 H H Me 1 -4-(cHx-CH₂O)Ph H H HH 6-6 H H Me 1 -(4-BzO-Ph) H H H H 6-7 H H Me 1 —C≡C—(CH₂)₂O-cHx H H H H6-8 H H Me 1 —C≡C—(CH₂)₂O-Ph H H H H 6-9 H H Me 2 —(CH₂)₃-cHx H H H H6-10 H H Me 2 —(CH₂)₃-Ph H H H H 6-11 H H Me 2 —(CH₂)₄-cHx H H H H 6-12H H Me 2 —(CH₂)₄-Ph H H H H 6-13 H H Me 2 —(CH₂)₅-cPn H H H H 6-14 H HMe 2 —(CH₂)₅-cHx H H H H 6-15 H H Me 2 —(CH₂)₅-cHx Me H H H 6-16 H H Me2 —(CH₂)₅-cHx H Me H H 6-17 H H Me 2 —(CH₂)₅-cHx F H H H 6-18 H H Me 2—(CH₂)₅-cHx H F H H 6-19 H Me Me 2 —(CH₂)₅-cHx H H H H 6-20 CO₂Me H Me 2—(CH₂)₅-cHx H H H H 6-21 CO₂Et H Me 2 —(CH₂)₅-cHx H H H H 6-22 H H Me 2—(CH₂)₅-(4-F-cHx) H H H H 6-23 H H Me 2 —(CH₂)₅-(4-Cl-cHx) H H H H 6-24H H Me 2 —(CH₂)₅-(4-Br-cHx) H H H H 6-25 H H Me 2 —(CH₂)₅-(4-Me-cHx) H HH H 6-26 H H Me 2 —(CH₂)₅-(4-Et-cHx) H H H H 6-27 H H Me 2—(CH₂)₅-(4-Pr-cHx) H H H H 6-28 H H Me 2 —(CH₂)₅-(4-iPr-cHx) H H H H6-29 H H Me 2 —(CH₂)₅-(4-CF₃-cHx) H H H H 6-30 H H Me 2—(CH₂)₅-(4-MeO-cHx) H H H H 6-31 H H Me 2 —(CH₂)₅-(4-EtO-cHx) H H H H6-32 H H Me 2 —(CH₂)₅-(4-PrO-cHx) H H H H 6-33 H H Me 2—(CH₂)₅-(4-iPrO-cHx) H H H H 6-34 H H Me 2 —(CH₂)₅-(3-MeS-cHx) H H H H6-35 H H Me 2 —(CH₂)₅-(4-MeS-cHx) H H H H 6-36 H H Me 2—(CH₂)₅-(6-4-diMe-cHx) H H H H 6-37 H H Me 2 —(CH₂)₅-(3,4-diMe-cHx) H HH H 6-38 H H Me 2 —(CH₂)₅-(3,5-diMe-cHx) H H H H 6-39 H H Me 2—(CH₂)₅-Ph H H H H 6-40 H H Me 2 —(CH₂)₅-Ph Me H H H 6-41 H H Me 2—(CH₂)₅-Ph H Me H H 6-42 H H Me 2 —(CH₂)₅-Ph F H H H 6-43 H H Me 2—(CH₂)₅-Ph H F H H 6-44 H Me Me 2 —(CH₂)₅-Ph H H H H 6-45 CO₂Me H Me 2—(CH₂)₅-Ph H H H H 6-46 CO₂Et H Me 2 —(CH₂)₅-Ph H H H H 6-47 H H Me 2—(CH₂)₅-(4-F-Ph) H H H H 6-48 H H Me 2 —(CH₂)₅-(4-Cl-Ph) H H H H 6-49 HH Me 2 —(CH₂)₅-(4-Br-Ph) H H H H 6-50 H H Me 2 —(CH₂)₅-(4-Me-Ph) H H H H6-51 H H Me 2 —(CH₂)₅-(4-Et-Ph) H H H H 6-52 H H Me 2 —(CH₂)₅-(4-Pr-Ph)H H H H 6-53 H H Me 2 —(CH₂)₅-(4-iPr-Ph) H H H H 6-54 H H Me 2—(CH₂)₅-(4-Bu-Ph) H H H H 6-55 H H Me 2 —(CH₂)₅-(4-CF₃-Ph) H H H H 6-56H H Me 2 —(CH₂)₅-(4-MeO-Ph) H H H H 6-57 H H Me 2 —(CH₂)₅-(4-EtO-Ph) H HH H 6-58 H H Me 2 —(CH₂)₅-(4-PrO-Ph) H H H H 6-59 H H Me 2—(CH₂)₅-(4-iPrO-Ph) H H H H 6-60 H H Me 2 —(CH₂)₅-(3-MeS-Ph) H H H H6-61 H H Me 2 —(CH₂)₅-(4-MeS-Ph) H H H H 6-62 H H Me 2—(CH₂)₅-(6-4-diMe-Ph) H H H H 6-63 H H Me 2 —(CH₂)₅-(3,4-diMe-Ph) H H HH 6-64 H H Me 2 —(CH₂)₅-(3,5-diMe-Ph) H H H H 6-65 H H Me 2 —(CH₂)₆-cPnH H H H 6-66 H H Me 2 —(CH₂)₆-cHx H H H H 6-67 H H Me 2 —(CH₂)₆-cHx Me HH H 6-68 H H Me 2 —(CH₂)₆-cHx H Me H H 6-69 H H Me 2 —(CH₂)₆-cHx F H H H6-70 H H Me 2 —(CH₂)₆-cHx H F H H 6-71 H Me Me 2 —(CH₂)₆-cHx H H H H6-72 CO₂Me H Me 2 —(CH₂)₆-cHx H H H H 6-73 CO₂Et H Me 2 —(CH₂)₆-cHx H HH H 6-74 H H Me 2 —(CH₂)₆-(4-F-cHx) H H H H 6-75 H H Me 2—(CH₂)₆-(4-Cl-cHx) H H H H 6-76 H H Me 2 —(CH₂)₆-(4-Br-cHx) H H H H 6-77H H Me 2 —(CH₂)₆-(4-Me-cHx) H H H H 6-78 H H Me 2 —(CH₂)6-(4-Et-cHx) H HH H 6-79 H H Me 2 —(CH₂)₆-(4-Pr-cHx) H H H H 6-80 H H Me 2—(CH₂)₆-(4-iPr-cHx) H H H H 6-81 H H Me 2 —(CH₂)₆-(4-Bu-cHx) H H H H6-82 H H Me 2 —(CH₂)₆-(4-CF₃-cHx) H H H H 6-83 H H Me 2—(CH₂)₆-(4-MeO-cHx) H H H H 6-84 H H Me 2 —(CH₂)₆-(4-EtO-cHx) H H H H6-85 H H Me 2 —(CH₂)₆-(4-PrO-cHx) H H H H 6-86 H H Me 2—(CH₂)₆-(4-iPrO-cHx) H H H H 6-87 H H Me 2 —(CH₂)₆-(3-MeS-cHx) H H H H6-88 H H Me 2 —(CH₂)₆-(4-MeS-cHx) H H H H 6-89 H H Me 2—(CH₂)₆-(6-4-diMe-cHx) H H H H 6-90 H H Me 2 —(CH₂)₆-(3,4-diMe-cHx) H HH H 6-91 H H Me 2 —(CH₂)₆-(3,5-diMe-cHx) H H H H 6-92 H H Me 2—(CH₂)₆-Ph H H H H 6-93 H H Me 2 —(CH₂)₆-Ph Me H H H 6-94 H H Me 2—(CH₂)₆-Ph H Me H H 6-95 H H Me 2 —(CH₂)₆-Ph F H H H 6-96 H H Me 2—(CH₂)₆-Ph H F H H 6-97 H Me Me 2 —(CH₂)₆-Ph H H H H 6-98 CO₂Me H Me 2—(CH₂)₆-Ph H H H H 6-99 CO₂Et H Me 2 —(CH₂)₆-Ph H H H H 6-100 H H Me 2—(CH₂)₆-(4-F-Ph) H H H H 6-101 H H Me 2 —(CH₂)₆-(4-Cl-Ph) H H H H 6-102H H Me 2 —(CH₂)₆-(4-Br-Ph) H H H H 6-103 H H Me 2 —(CH₂)₆-(4-Me-Ph) H HH H 6-104 H H Me 2 —(CH₂)₆-(4-Et-Ph) H H H H 6-105 H H Me 2—(CH₂)₆-(4-Pr-Ph) H H H H 6-106 H H Me 2 —(CH₂)₆-(4-iPr-Ph) H H H H6-107 H H Me 2 —(CH₂)₆-(4-Bu-Ph) H H H H 6-108 H H Me 2—(CH₂)₆-(4-CF₃-Ph) H H H H 6-109 H H Me 2 —(CH₂)₆-(4-MeO-Ph) H H H H6-110 H H Me 2 —(CH₂)₆-(4-EtO-Ph) H H H H 6-111 H H Me 2—(CH₂)₆-(4-PrO-Ph) H H H H 6-112 H H Me 2 —(CH₂)₆-(4-iPrO-Ph) H H H H6-113 H H Me 2 —(CH₂)₆-(3-MeS-Ph) H H H H 6-114 H H Me 2—(CH₂)₆-(4-MeS-Ph) H H H H 6-115 H H Me 2 —(CH₂)₆-(6-4-diMe-Ph) H H H H6-116 H H Me 2 —(CH₂)₆-(3,4-diMe-Ph) H H H H 6-117 H H Me 2—(CH₂)₆-(3,5-diMe-Ph) H H H H 6-118 H H Me 2 —(CH₂)₇-cHx H H H H 6-119 HH Me 2 —(CH₂)₇-Ph H H H H 6-120 H H Me 2 —(CH₂)₈-cHx H H H H 6-121 H HMe 2 —(CH₂)₈-Ph H H H H 6-122 H H Me 2 —CH═CH—(CH₂)₃-cHx H H H H 6-123 HMe Me 2 —CH═CH—(CH₂)₃-cHx H H H H 6-124 CO₂Me H Me 2 —CH═CH—(CH₂)₃-cHx HH H H 6-125 CO₂Et H Me 2 —CH═CH—(CH₂)₃-cHx H H H H 6-126 H H Me 2—CH═CH—(CH₂)₃-Ph H H H H 6-127 H Me Me 2 —CH═CH—(CH₂)₃-Ph H H H H 6-128CO₂Me H Me 2 —CH═CH—(CH₂)₃-Ph H H H H 6-129 CO₂Et H Me 2—CH═CH—(CH₂)₃-Ph H H H H 6-130 H H Me 2 —CH═CH—(CH₂)₄-cHx H H H H 6-131H Me Me 2 —CH═CH—(CH₂)₄-cHx H H H H 6-132 CO₂Me H Me 2 —CH═CH—(CH₂)₄-cHxH H H H 6-133 CO₂Et H Me 2 —CH═CH—(CH₂)₄-cHx H H H H 6-134 H H Me 2—CH═CH—(CH₂)₄-Ph H H H H 6-135 H Me Me 2 —CH═CH—(CH₂)₄-Ph H H H H 6-136CO₂Me H Me 2 —CH═CH—(CH₂)₄-Ph H H H H 6-137 CO₂Et H Me 2—CH═CH—(CH₂)₄-Ph H H H H 6-138 H H Me 2 —C═C—CH₂O-cHx H H H H 6-139 H HMe 2 —C═C—CH₂O-Ph H H H H 6-140 H H Me 2 —C═C—(CH₂)₂O-cHx H H H H 6-141H H Me 2 —C═C—(CH₂)₂O-Ph H H H H 6-142 H H Me 2 —C≡C—CH₂-cHx H H H H6-143 H Me Me 2 —C≡C—CH₂-cHx H H H H 6-144 CO₂Me H Me 2 —C≡C—CH₂-cHx H HH H 6-145 CO₂Et H Me 2 —C≡C—CH₂-cHx H H H H 6-146 H H Me 2 —C≡C—CH₂-Ph HH H H 6-147 H Me Me 2 —C≡C—CH₂-Ph H H H H 6-148 CO₂Me H Me 2 —C≡C—CH₂-PhH H H H 6-149 CO₂Et H Me 2 —C≡C—CH₂-Ph H H H H 6-150 H H Me 2—C≡C—(CH₂)₂-cHx H H H H 6-151 H Me Me 2 —C≡C—(CH₂)₂-cHx H H H H 6-152CO₂Me H Me 2 —C≡C—(CH₂)₂-cHx H H H H 6-153 CO₂Et H Me 2 —C≡C—(CH₂)₂-cHxH H H H 6-154 H H Me 2 —C≡C—(CH₂)₂-Ph H H H H 6-155 H Me Me 2—C≡C—(CH₂)₂-Ph H H H H 6-156 CO₂Me H Me 2 —C≡C—(CH₂)₂-Ph H H H H 6-157CO₂Et H Me 2 —C≡C—(CH₂)₂-Ph H H H H 6-158 H H Me 2 —C≡C—(CH₂)₃-cPn H H HH 6-159 H H Me 2 —C≡C—(CH₂)₃-cHx H H H H 6-160 H H Me 2 —C≡C—(CH₂)₃-cHxMe H H H 6-161 H H Me 2 —C≡C—(CH₂)₃-cHx H Me H H 6-162 H H Me 2—C≡C—(CH₂)₃-cHx F H H H 6-163 H H Me 2 —C≡C—(CH₂)₃-cHx H F H H 6-164 HMe Me 2 —C≡C—(CH₂)₃-cHx H H H H 6-165 CO₂Me H Me 2 —C≡C—(CH₂)₃-cHx H H HH 6-166 CO₂Et H Me 2 —C≡C—(CH₂)₃-cHx H H H H 6-167 H H Me 2—C≡C—(CH₂)₃-(4-F-cHx) H H H H 6-168 H H Me 2 —C≡C—(CH₂)₃-(4-Cl-cHx) H HH H 6-169 H H Me 2 —C≡C—(CH₂)₃-(4-Br-cHx) H H H H 6-170 H H Me 2—C≡C—(CH₂)₃-(4-Me-cHx) H H H H 6-171 H H Me 2 —C≡C—(CH₂)₃-(4-Et-cHx) H HH H 6-172 H H Me 2 —C≡C—(CH₂)₃-(4-Pr-cHx) H H H H 6-173 H H Me 2—C≡C—(CH₂)₃-(4-iPr-cHx) H H H H 6-174 H H Me 2 —C≡C—(CH₂)₃-(4-Bu-cHx) HH H H 6-175 H H Me 2 —C≡C—(CH₂)₃-(4-CF₃-cHx) H H H H 6-176 H H Me 2—C≡C—(CH₂)₃-(4-MeO-cHx) H H H H 6-177 H H Me 2 —C≡C—(CH₂)₃-(4-EtO-cHx) HH H H 6-178 H H Me 2 —C≡C—(CH₂)₃-(4-PrO-cHx) H H H H 6-179 H H Me 2—C≡C—(CH₂)₃-(4-iPrO-cHx) H H H H 6-180 H H Me 2 —C≡C—(CH₂)₃-(3-MeS-cHx)H H H H 6-181 H H Me 2 —C≡C—(CH₂)₃-(4-MeS-cHx) H H H H 6-182 H H Me 2—C≡C—(CH₂)₃-(6-4-diMe-cHx) H H H H 6-183 H H Me 2—C≡C—(CH₂)₃-(3,4-diMe-cHx) H H H H 6-184 H H Me 2—C≡C—(CH₂)₃-(3,5-diMe-cHx) H H H H 6-185 H H Me 2 —C≡C—(CH₂)₃-Ph H H H H6-186 H H Me 2 —C≡C—(CH₂)₃-Ph Me H H H 6-187 H H Me 2 —C≡C—(CH₂)₃-Ph HMe H H 6-188 H H Me 2 —C≡C—(CH₂)₃-Ph F H H H 6-189 H H Me 2—C≡C—(CH₂)₃-Ph H F H H 6-190 H Me Me 2 —C≡C—(CH₂)₃-Ph H H H H 6-191CO₂Me H Me 2 —C≡C—(CH₂)₃-Ph H H H H 6-192 CO₂Et H Me 2 —C≡C—(CH₂)₃-Ph HH H H 6-193 H H Me 2 —C≡C—(CH₂)₃-(4-F-Ph) H H H H 6-194 H H Me 2—C≡C—(CH₂)₃-(4-Cl-Ph) H H H H 6-195 H H Me 2 —C≡C—(CH₂)₃-(4-Br-Ph) H H HH 6-196 H H Me 2 —C≡C—(CH₂)₃-(4-Me-Ph) H H H H 6-197 H H Me 2—C≡C—(CH₂)₃-(4-Et-Ph) H H H H 6-198 H H Me 2 —C≡C—(CH₂)₃-(4-Pr-Ph) H H HH 6-199 H H Me 2 —C≡C—(CH₂)₃-(4-iPr-Ph) H H H H 6-200 H H Me 2—C≡C—(CH₂)₃-(4-Bu-Ph) H H H H 6-201 H H Me 2 —C≡C—(CH₂)₃-(4-CF₃-Ph) H HH H 6-202 H H Me 2 —C≡C—(CH₂)₃-(4-MeO-Ph) H H H H 6-203 H H Me 2—C≡C—(CH₂)₃-(4-EtO-Ph) H H H H 6-204 H H Me 2 —C≡C—(CH₂)₃-(4-PrO-Ph) H HH H 6-205 H H Me 2 —C≡C—(CH₂)₃-(4-iPrO-Ph) H H H H 6-206 H H Me 2—C≡C—(CH₂)₃-(3-MeS-Ph) H H H H 6-207 H H Me 2 —C≡C—(CH₂)₃-(4-MeS-Ph) H HH H 6-208 H H Me 2 —C≡C—(CH₂)₃-(6-4-diMe-Ph) H H H H 6-209 H H Me 2—C≡C—(CH₂)₃-(3,4-diMe-Ph) H H H H 6-210 H H Me 2—C≡C—(CH₂)₃-(3,5-diMe-Ph) H H H H 6-211 H H Me 2 —C≡C—(CH₂)₄-cPn H H H H6-212 H H Me 2 —C≡C—(CH₂)₄-cHx H H H H 6-213 H H Me 2 —C≡C—(CH₂)₄-cHx MeH H H 6-214 H H Me 2 —C≡C—(CH₂)₄-cHx H Me H H 6-215 H H Me 2—C≡C—(CH₂)₄-cHx F H H H 6-216 H H Me 2 —C≡C—(CH₂)₄-cHx H F H H 6-217 HMe Me 2 —C≡C—(CH₂)₄-cHx H H H H 6-218 CO₂Me H Me 2 —C≡C—(CH₂)₄-cHx H H HH 6-219 CO₂Et H Me 2 —C≡C—(CH₂)₄-cHx H H H H 6-220 H H Me 2—C≡C—(CH₂)₄-(4-F-cHx) H H H H 6-221 H H Me 2 —C≡C—(CH₂)₄-(4-Cl-cHx) H HH H 6-222 H H Me 2 —C≡C—(CH₂)₄-(4-Br-cHx) H H H H 6-223 H H Me 2—C≡C—(CH₂)₄-(4-Me-cHx) H H H H 6-224 H H Me 2 —C≡C—(CH₂)₄-(4-Et-cHx) H HH H 6-225 H H Me 2 —C≡C—(CH₂)₄-(4-Pr-cHx) H H H H 6-226 H H Me 2—C≡C—(CH₂)₄-(4-iPr-cHx) H H H H 6-227 H H Me 2 —C≡C—(CH₂)₄-(4-Bu-cHx) HH H H 6-228 H H Me 2 —C≡C—(CH₂)₄-(4-CF₃-cHx) H H H H 6-229 H H Me 2—C≡C—(CH₂)₄-(4-MeO-cHx) H H H H 6-230 H H Me 2 —C≡C—(CH₂)₄-(4-EtO-cHx) HH H H 6 231 H H Me 2 —C≡C—(CH₂)₄-(4-PrO-cHx) H H H H 6-232 H H Me 2—C≡C—(CH₂)₄-(4-iPrO-cHx) H H H H 6-233 H H Me 2 —C≡C—(CH₂)₄-(4-MeS-cHx)H H H H 6-234 H H Me 2 —C≡C—(CH₂)₄-(6-4-diMe-cHx) H H H H 6-235 H H Me 2—C≡C—(CH₂)₄-(3,4-diMe-cHx) H H H H 6-236 H H Me 2—C≡C—(CH₂)₄-(3,5-diMe-cHx) H H H H 6-237 H H Me 2 —C≡C—(CH₂)₄-Ph H H H H6-238 H H Me 2 —C≡C—(CH₂)₄-Ph Me H H H 6-239 H H Me 2 —C≡C—(CH₂)₄-Ph HMe H H 6-240 H H Me 2 —C≡C—(CH₂)₄-Ph F H H H 6-241 H H Me 2—C≡C—(CH₂)₄-Ph H F H H 6-242 H Me Me 2 —C≡C—(CH₂)₄-Ph H H H H 6-243CO₂Me H Me 2 —C≡C—(CH₂)₄-Ph H H H H 6-244 CO₂Et H Me 2 —C≡C—(CH₂)₄-Ph HH H H 6-245 H H Me 2 —C≡C—(CH₂)₄-(4-F-Ph) H H H H 6-246 H H Me 2—C≡C—(CH₂)₄-(4-Cl-Ph) H H H H 6-247 H H Me 2 —C≡C—(CH₂)₄-(4-Br-Ph) H H HH 6-248 H H Me 2 —C≡C—(CH₂)₄-(4-Me-Ph) H H H H 6-249 H H Me 2—C≡C—(CH₂)₄-(4-Et-Ph) H H H H 6-250 H H Me 2 —C≡C—(CH₂)₄-(4-Pr-Ph) H H HH 6-251 H H Me 2 —C≡C—(CH₂)₄-(4-iPr-Ph) H H H H 6-252 H H Me 2—C≡C—(CH₂)₄-(4-Bu-Ph) H H H H 6-253 H H Me 2 —C≡C—(CH₂)₄-(4-CF₃-Ph) H HH H 6-254 H H Me 2 —C≡C—(CH₂)₄-(4-MeO-Ph) H H H H 6-255 H H Me 2—C≡C—(CH₂)₄-(4-EtO-Ph) H H H H 6-256 H H Me 2 —C≡C—(CH₂)₄-(4-PrO-Ph) H HH H 6-257 H H Me 2 —C≡C—(CH₂)₄-(4-iPrO-Ph) H H H H 6-258 H H Me 2—C≡C—(CH₂)₄-(3-MeS-Ph) H H H H 6-259 H H Me 2 —C≡C—(CH₂)₄-(4-MeS-Ph) H HH H 6-260 H H Me 2 —C≡C—(CH₂)₄-(6-4-diMe-Ph) H H H H 6-261 H H Me 2—C≡C—(CH₂)₄-(3,4-diMe-Ph) H H H H 6-262 H H Me 2—C≡C—(CH₂)₄-(3,5-diMe-Ph) H H H H 6-263 H H Me 2 —C≡C—(CH₂)₅-cHx H H H H6-264 H Me Me 2 —C≡C—(CH₂)₅-cHx H H H H 6-265 CO₂Me H Me 2—C≡C—(CH₂)₅-cHx H H H H 6-266 CO₂Et H Me 2 —C≡C—(CH₂)₅-cHx H H H H 6-267H H Me 2 —C≡C—(CH₂)₅-Ph H H H H 6-268 H Me Me 2 —C≡C—(CH₂)₅-Ph H H H H6-269 CO₂Me H Me 2 —C≡C—(CH₂)₅-Ph H H H H 6-270 CO₂Et H Me 2—C≡C—(CH₂)₅-Ph H H H H 6-271 H H Me 2 —C≡C—(CH₂)₆-cHx H H H H 6-272 H MeMe 2 —C≡C—(CH₂)₆-cHx H H H H 6-273 CO₂Me H Me 2 —C≡C—(CH₂)₆-cHx H H H H6-274 CO₂Et H Me 2 —C≡C—(CH₂)₆-cHx H H H H 6-275 H H Me 2 —C≡C—(CH₂)₆-PhH H H H 6-276 H Me Me 2 —C≡C—(CH₂)₆-Ph H H H H 6-277 CO₂Me H Me 2—C≡C—(CH₂)₆-Ph H H H H 6-278 CO₂Et H Me 2 —C≡C—(CH₂)₆-Ph H H H H 6-279 HH Me 2 —C≡C—CH₂O-cHx H H H H 6-280 H Me Me 2 —C≡C—CH₂O-cHx H H H H 6-281CO₂Me H Me 2 —C≡C—CH₂O-cHx H H H H 6-282 CO₂Et H Me 2 —C≡C—CH₂O-cHx H HH H 6-283 H H Me 2 —C≡C—CH₂O-Ph H H H H 6-284 H Me Me 2 —C≡C—CH₂O-Ph H HH H 6-285 CO₂Me H Me 2 —C≡C—CH₂O-Ph H H H H 6-286 CO₂Et H Me 2—C≡C—CH₂O-Ph H H H H 6-287 H H Me 2 —C≡C—(CH₂)₂O-cPn H H H H 6-288 H HMe 2 —C≡C—(CH₂)₂O-cHx H H H H 6-289 H H Me 2 —C≡C—(CH₂)₂O-cHx Me H H H6-290 H H Me 2 —C≡C—(CH₂)₂O-cHx H Me H H 6-291 H H Me 2 —C≡C—(CH₂)₂O-cHxF H H H 6-292 H H Me 2 —C≡C—(CH₂)₂O-cHx H F H H 6-293 H Me Me 2—C≡C—(CH₂)₂—OCH₂-cHx H H H H 6-294 CO₂Me H Me 2 —C≡C—(CH₂)₂O-cHx H H H H6-295 CO₂Et H Me 2 —C≡C—(CH₂)₂O-cHx H H H H 6-296 H H Me 2—C≡C—(CH₂)₂O-(4-F-cHx) H H H H 6-297 H H Me 2 —C≡C—(CH₂)₂O-(4-Cl-cHx) HH H H 6-298 H H Me 2 —C≡C—(CH₂)₂O-(4-Br-cHx) H H H H 6-299 H H Me 2—C≡C—(CH₂)₂O-(4-Me-cHx) H H H H 6-300 H H Me 2 —C≡C—(CH₂)₂O-(4-Et-cHx) HH H H 6-301 H H Me 2 —C≡C—(CH₂)₂O-(4-Pr-cHx) H H H H 6-302 H H Me 2—C≡C—(CH₂)₂O-(4-iPr-cHx) H H H H 6-303 H H Me 2 —C≡C—(CH₂)₂O-(4-Bu-cHx)H H H H 6-304 H H Me 2 —C≡C—(CH₂)₂O-(4-CF₃-cHx) H H H H 6-305 H H Me 2—C≡C—(CH₂)₂O-(4-MeO-cHx) H H H H 6-306 H H Me 2 —C≡C—(CH₂)₂O(4-EtO-cHx)H H H H 6-307 H H Me 2 —C≡C—(CH₂)₂O-(4-PrO-cHx) H H H H 6-308 H H Me 2—C≡C—(CH₂)₂O-(4-iPrO-cHx) H H H H 6-309 H H Me 2—C≡C—(CH₂)₂O-(3-MeS-cHx) H H H H 6-310 H H Me 2 —C≡C—(CH₂)₂O-(4-MeS-cHx)H H H H 6-311 H H Me 2 —C≡C—(CH₂)₂O-(6-4- H H H H diMe-cHx) 6-312 H H Me2 —C≡C—(CH₂)₂O-(3,4- H H H H diMe-cHx) 6-313 H H Me 2 —C≡C—(CH₂)₂O-(3,5-H H H H diMe-cHx) 6-314 H H Me 2 —C≡C—(CH₂)₂O-Ph H H H H 6-315 H H Me 2—C≡C-(CH₂)₂O-Ph Me H H H 6-316 H H Me 2 —C≡C—(CH₂)₂O-Ph H Me H H 6-317 HH Me 2 —C≡C—(CH₂)₂O-Ph F H H H 6-318 H H Me 2 —C≡C—(CH₂)₂O-Ph H F H H6-319 H Me Me 2 —C≡C—(CH₂)₂-OCH₂-Ph H H H H 6-320 CO₂Me H Me 2—C≡C—(CH₂)₂O-Ph H H H H 6-321 CO₂Et H Me 2 —C≡C—(CH₂)₂O-Ph H H H H 6-322H H Me 2 —C≡C—(CH₂)₂O-(4-F-Ph) H H H H 6-323 H H Me 2—C≡C—(CH₂)₂O-(4-Cl-Ph) H H H H 6-324 H H Me 2 —C≡C—(CH₂)₂O-(4-Br-Ph) H HH H 6-325 H H Me 2 —C≡C—(CH₂)₂O-(4-Me-Ph) H H H H 6-326 H H Me 2—C≡C—(CH₂)₂O-(4-Et-Ph) H H H H 6-327 H H Me 2 —C≡C—(CH₂)₂O-(4-Pr-Ph) H HH H 6-328 H H Me 2 —C≡C—(CH₂)₂O-(4-iPr-Ph) H H H H 6-329 H H Me 2—C≡C—(CH₂)₂O-(4-Bu-Ph) H H H. H 6-330 H H Me 2 —C≡C—(CH₂)₂O-(4-CF₃-Ph) HH H H 6-331 H H Me 2 —C≡C—(CH₂)₂O-(4-MeO-Ph) H H H H 6-332 H H Me 2—C≡C—(CH₂)₂O-(4-EtO-Ph) H H H H 6-333 H H Me 2 —C≡C—(CH₂)₂O-(4-PrO-Ph) HH H H 6-334 H H Me 2 —C≡C—(CH₂)₂O-(4-iPrO-Ph) H H H H 6-335 H H Me 2—C≡C—(CH₂)₂O-(4-MeS-Ph) H H H H 6-336 H H Me 2—C≡C—(CH₂)₂O-(6-4-diMe-Ph) H H H H 6-337 H H Me 2—C≡C—(CH₂)₂O-(3,4-diMe-Ph) H H H H 6-338 H H Me 2—C≡C—(CH₂)₂O-(3,5-diMe-Ph) H H H H 6-339 H H Me 2 —CO—(CH₂)₄-cHx H H H H6-340 H Me Me 2 —CO—(CH₂)₄-cHx H H H H 6-341 CO₂Me H Me 2 —CO—(CH₂)₄-cHxH H H H 6-342 CO₂Et H Me 2 —CO—(CH₂)₄-cHx H H H H 6-343 H H Me 2—CO—(CH₂)₄-Ph H H H H 6-344 H Me Me 2 —CO—(CH₂)₄-Ph H H H H 6-345 CO₂MeH Me 2 —CO—(CH₂)₄-Ph H H H H 6-346 CO₂Et H Me 2 —CO—(CH₂)₄-Ph H H H H6-347 H H Me 2 —CO—(CH₂)₅-cHx H H H H 6-348 H Me Me 2 —CO—(CH₂)₅-cHx H HH H 6-349 CO₂Me H Me 2 —CO—(CH₂)₅-cHx H H H H 6-350 CO₂Et H Me 2—CO—(CH₂)₅-cHx H H H H 6-351 H H Me 2 —CO—(CH₂)₅-Ph H H H H 6-352 H MeMe 2 —CO—(CH₂)₅-Ph H H H H 6-353 CO₂Me H Me 2 —CO—(CH₂)₅-Ph H H H H6-354 CO₂Et H Me 2 —CO—(CH₂)₅-Ph H H H H 6-355 H H Me 2—CH(OH)—(CH₂)₄-cHx H H H H 6-356 H Me Me 2 —CH(OH)—(CH₂)₄-cHx H H H H6-357 CO₂Me H Me 2 —CH(OH)—(CH₂)₄-cHx H H H H 6-358 CO₂Et H Me 2—CH(OH)—(CH₂)₄-cHx H H H H 6-359 H H Me 2 —CH(OH)—(CH₂)₄-Ph H H H H6-360 H Me Me 2 —CH(OH)—(CH₂)₄-Ph H H H H 6-361 CO₂Me H Me 2—CH(OH)—(CH₂)₄-Ph H H H H 6-362 CO₂Et H Me 2 —CH(OH)—(CH₂)₄-Ph H H H H6-363 H H Me 2 —CH(OH)—(CH₂)₅-cHx H H H H 6-364 H Me Me 2—CH(OH)—(CH₂)₅-cHx H H H H 6-365 CO₂Me H Me 2 —CH(OH)—(CH₂)₅-cHx H H H H6-366 CO₂Et H Me 2 —CH(OH)—(CH₂)₅-cHx H H H H 6-367 H H Me 2—CH(OH)—(CH₂)₅-Ph H H H H 6-368 H Me Me 2 —CH(OH)—(CH₂)₅-Ph H H H H6-369 CO₂Me H Me 2 —CH(OH)—(CH₂)₅-Ph H H H H 6-370 CO₂Et H Me 2—CH(OH)—(CH₂)₅-Ph H H H H 6-371 H H Me 2 -4-(cHx-CH₂O)Ph H H H H 6-372 HMe Me 2 -4-(cHx-CH₂O)Ph H H H H 6-373 CO₂Me H Me 2 -4-(cHx-CH₂O)Ph H H HH 6-374 CO₂Et H Me 2 -4-(cHx-CH₂O)Ph H H H H 6-375 H H Me 2-4-[cHx-(CH₂)₂O]Ph H H H H 6-376 H H Me 2 -4-[cHx-(CH₂)₃O]Ph H H H H6-377 H H Me 2 -(4-BzO-Ph) H H H H 6-378 H Me Me 2 -(4-BzO-Ph) H H H H6-379 CO₂Me H Me 2 -(4-BzO-Ph) H H H H 6-380 CO₂Et H Me 2 -(4-BzO-Ph) HH H H 6-381 H H Me 2 -(4-BzO-2-F-Ph) H H H H 6-382 H H Me 2-(4-BzO-3-F-Ph) H H H H 6-383 H H Me 2 -(4-BzO-6-3-diF-Ph) H H H H 6-384H H Me 2 -(4-BzO-2-Cl-Ph) H H H H 6-385 H H Me 2 -(4-BzO-3-Cl-Ph) H H HH 6-386 H H Me 2 -(4-BzO-6-3-diCl-Ph) H H H H 6-387 H H Me 2-(4-BzO-2-Me-Ph) H H H H 6-388 H H Me 2 -(4-BzO-3-Me-Ph) H H H H 6-389 HH Me 2 -(4-BzO-6-3-diMe-Ph) H H H H 6-390 H H Me 2 -4-[Ph-(CH₂)₂O]-Ph HH H H 6-391 H H Me 2 -4-[Ph-(CH₂)₃O]-Ph H H H H 6-392 H H Et 2—(CH₂)₅-cHx H H H H 6-393 H H Et 2 —(CH₂)₆-cHx H H H H 6-394 H H Et 2—C≡C—(CH₂)₃-cHx H H H H 6-395 H H Et 2 —C≡C—(CH₂)₄-cHx H H H H 6-396 H HEt 2 -4-(cHx-CH₂O)Ph H H H H 6-397 H H Et 2 -(4-BzO-Ph) H H H H 6-398 HH Et 2 —C≡C—(CH₂)₂O-cHx H H H H 6-399 H H Et 2 —C≡C—(CH₂)₂O-Ph H H H H6-400 H H Pr 2 —(CH₂)₅-cHx H H H H 6-401 H H Pr 2 —(CH₂)₆-cHx H H H H6-402 H H Pr 2 —C≡C—(CH₂)₃-cHx H H H H 6-403 H H Pr 2 —C≡C—(CH₂)₄-cHx HH H H 6-404 H H Pr 2 -4-(cHx-CH₂O)Ph H H H H 6-405 H H Pr 2 -(4-BzO-Ph)H H H H 6-406 H H Pr 2 —C≡C—(CH₂)₂O-cHx H H H H 6-407 H H Pr 2—C≡C—(CH₂)₂O-Ph H H H H 6-408 H H Me 3 —(CH₂)₅-cHx H H H H 6-409 H H Me3 —(CH₂)₆-cHx H H H H 6-410 H H Me 3 —C≡C—(CH₂)₃-cHx H H H H 6-411 H HMe 3 —C≡C—(CH₂)₄-cHx H H H H 6-412 H H Me 3 -4-(cHx-CH₂O)Ph H H H H6-413 H H Me 3 -(4-BzO-Ph) H H H H 6-414 H H Me 3 —C≡C—(CH₂)₂O-cHx H H HH 6-415 H H Me 3 —C≡C—(CH₂)₂OPh H H H H 6-416 COCH₃ H Me 2 —(CH₂)₄-cHx HH H H 6-417 COC₂H₅ H Me 2 —(CH₂)₄-cHx H H H H 6-418 COC₃H₇ H Me 2—(CH₂)₄-cHx H H H H 6-419 COC₄H₉ H Me 2 —(CH₂)₄-cHx H H H H 6-420COC₅H₁₁ H Me 2 —(CH₂)₄-cHx H H H H 6-421 COC₆H₁₃ H Me 2 —(CH₂)₄-cHx H HH H 6-422 COC₇H₁₅ H Me 2 —(CH₂)₄-cHx H H H H 6-423 COC₈H₁₇ H Me 2—(CH₂)₄-cHx H H H H 6-424 COCH₃ H Me 2 —(CH₂)₄-Ph H H H H 6-425 COC₂H₅ HMe 2 —(CH₂)₄-Ph H H H H 6-426 COC₃H₇ H Me 2 —(CH₂)₄-Ph H H H H 6-427COC₄H₉ H Me 2 —(CH₂)₄-Ph H H H H 6-428 COC₅H₁₁ H Me 2 —(CH₂)₄-Ph H H H H6-429 COC₆H₁₃ H Me 2 —(CH₂)₄-Ph H H H H 6-430 COC₇H₁₅ H Me 2 —(CH₂)₄-PhH H H H 6-431 COC₈H₁₇ H Me 2 —(CH₂)₄-Ph H H H H 6-432 COCH₃ H Me 2—(CH₂)₅-cHx H H H H 6-433 COC₂H₅ H Me 2 —(CH₂)₅-cHx H H H H 6-434 COC₃H₇H Me 2 —(CH₂)₅-cHx H H H H 6-435 COC₄H₉ H Me 2 —(CH₂)₅-cHx H H H H 6-436COC₅H₁₁ H Me 2 —(CH₂)₅-cHx H H H H 6-437 COC₆H₁₃ H Me 2 —(CH₂)₅-cHx H HH H 6-438 COC₇H₁₅ H Me 2 —(CH₂)₅-cHx H H H H 6-439 COC₈H₁₇ H Me 2—(CH₂)₅-cHx H H H H 6-440 COCH₃ H Me 2 —(CH₂)₅-Ph H H H H 6-441 COC₂H₅ HMe 2 —(CH₂)₅-Ph H H H H 6-442 COC₃H₇ H Me 2 —(CH₂)₅-Ph H H H H 6-443COC₄H₉ H Me 2 —(CH₂)₅-Ph H H H H 6-444 COC₅H₁₁ H Me 2 —(CH₂)₅-Ph H H H H6-445 COC₆H₁₃ H Me 2 —(CH₂)₅-Ph H H H H 6-446 COC₇H₁₅ H Me 2 —(CH₂)₅-PhH H H H 6-447 COC₈H₁₇ H Me 2 —(CH₂)₅-Ph H H H H 6-448 COCH₃ H Me 2—C≡C—(CH₂)₃-cHx H H H H 6-449 COC₂H₅ H Me 2 —C≡C—(CH₂)₃-cHx H H H H6-450 COC₃H₇ H Me 2 —C≡C—(CH₂)₃-cHx H H H H 6-451 COC₄H₉ H Me 2—C≡C—(CH₂)₃-cHx H H H H 6-452 COC₅H₁₁ H Me 2 —C≡C—(CH₂)₃-cHx H H H H6-453 COC₆H₁₃ H Me 2 —C≡C—(CH₂)₃-cHx H H H H 6-454 COC₇H₁₅ H Me 2—C≡C—(CH₂)₃-cHx H H H H 6-455 COC₈H₁₇ H Me 2 —C≡C—(CH₂)₃-cHx H H H H6-456 COCH₃ H Me 2 —C≡C—(CH₂)₃-Ph H H H H 6-457 COC₂H₅ H Me 2—C≡C—(CH₂)₃-Ph H H H H 6-458 COC₃H₇ H Me 2 —C≡C—(CH₂)₃-Ph H H H H 6-459COC₄H₉ H Me 2 —C≡C—(CH₂)₃-Ph H H H H 6-460 COC₅H₁₁ H Me 2 —C≡C—(CH₂)₃-PhH H H H 6-461 COC₆H₁₃ H Me 2 —C≡C—(CH₂)₃-Ph H H H H 6-462 COC₇H₁₅ H Me 2—C≡C—(CH₂)₃-Ph H H H H 6-463 COC₈H₁₇ H Me 2 —C≡C—(CH₂)₃-Ph H H H H 6-464COCH₃ H Me 2 —C≡C—(CH₂)₄-cHx H H H H 6-465 COC₂H₅ H Me 2 —C≡C—(CH₂)₄-cHxH H H H 6-466 COC₃H₇ H Me 2 —C≡C—(CH₂)₄-cHx H H H H 6-467 COC₄H₉ H Me 2—C≡C—(CH₂)₄-cHx H H H H 6-468 COC₅H₁₁ H Me 2 —C≡C—(CH₂)₄-cHx H H H H6-469 COC₆H₁₃ H Me 2 —C≡C—(CH₂)₄-cHx H H H H 6-470 COC₇H₁₅ H Me 2—C≡C—(CH₂)₄-cHx H H H H 6-471 COC₈H₁₇ H Me 2 —C≡C—(CH₂)₄-cHx H H H H6-472 COCH₃ H Me 2 —C≡C—(CH₂)₄-Ph H H H H 6-473 COC₂H₅ H Me 2—C≡C—(CH₂)₄-Ph H H H H 6-474 COC₃H₇ H Me 2 —C≡C—(CH₂)₄-Ph H H H H 6-475COC₄H₉ H Me 2 —C≡C—(CH₂)₄-Ph H H H H 6-476 COC₅H₁₁ H Me 2 —C≡C—(CH₂)₄-PhH H H H 6-477 COC₆H₁₃ H Me 2 —C≡C—(CH₂)₄-Ph H H H H 6-478 COC₇H₁₅ H Me 2—C≡C—(CH₂)₄-Ph H H H H 6-479 COC₆H₁₇ H Me 2 —C≡C—(CH₂)₄-Ph H H H H 6-480COCH₃ H Me 2 —C≡C—(CH₂)₂O-cHx H H H H 6-481 COC₂H₅ H Me 2—C≡C—(CH₂)₂O-cHx H H H H 6-482 COC₃H₇ H Me 2 —C≡C—(CH₂)₂O-cHx H H H H6-483 COC₄H₉ H Me 2 —C≡C—(CH₂)₂O-cHx H H H H 6-484 COC₅H₁₁ H Me 2—C≡C—(CH₂)₂O-cHx H H H H 6-485 COC₆H₁₃ H Me 2 —C≡C—(CH₂)₂O-cHx H H H H6-486 COC₇H₁₅ H Me 2 —C≡C—(CH₂)₂O-cHx H H H H 6-487 COC₈H₁₇ H Me 2—C≡C—(CH₂)₂O-cHx H H H H 6-488 COCH₃ H Me 2 —C≡C—(CH₂)₂O-Ph H H H H6-489 COC₂H₅ H Me 2 —C≡C—(CH₂)₂O-Ph H H H H 6-490 COC₃H₇ H Me 2—C≡C—(CH₂)₂O-Ph H H H H 6-491 COC₄H₉ H Me 2 —C≡C—(CH₂)₂O-Ph H H H H6-492 COC₅H₁₁ H Me 2 —C≡C—(CH₂)₂O-Ph H H H H 6-493 COC₆H₁₃ H Me 2—C≡C—(CH₂)₂O-Ph H H H H 6-494 COC₇H₁₅ H Me 2 —C≡C—(CH₂)₂O-Ph H H H H6-495 COC₈H₁₇ H Me 2 —C≡C—(CH₂)₂O-Ph H H H H 6-496 COCH₃ H Me 2—CO—(CH₂)₄-cHx H H H H 6-497 COC₂H₅ H Me 2 —CO—(CH₂)₄-cHx H H H H 6-498COC₃H₇ H Me 2 —CO—(CH₂)₄-cHx H H H H 6-499 COC₄H₉ H Me 2 —CO—(CH₂)₄-cHxH H H H 6-500 COC₅H₁₁ H Me 2 —CO—(CH₂)₄-cHx H H H H 6-501 COC₆H₁₃ H Me 2—CO—(CH₂)₄-cHx H H H H 6-502 COC₇H₁₅ H Me 2 —CO—(CH₂)₄-cHx H H H H 6-503COC₈H₁₇ H Me 2 —CO—(CH₂)₄-cHx H H H H 6-504 COCH₃ H Me 2 —CO—(CH₂)₄-Ph HH H H 6-505 COC₂H₅ H Me 2 —CO—(CH₂)₄-Ph H H H H 6-506 COC₃H₇ H Me 2—CO—(CH₂)₄-Ph H H H H 6-507 COC₄H₉ H Me 2 —CO—(CH₂)₄-Ph H H H H 6-508COC₅H₁₁ H Me 2 —CO—(CH₂)₄-Ph H H H H 6-509 COC₆H₁₃ H Me 2 —CO—(CH₂)₄-PhH H H H 6-510 COC₇H₁₅ H Me 2 —CO—(CH₂)₄-Ph H H H H 6-511 COC₈H₁₇ H Me 2—CO—(CH₂)₄-Ph H H H H

TABLE 7

Compd. R¹ R² R⁴ n —Y—Z—R⁵ R⁶ R⁷ R¹⁰ R¹¹ 7-1 H H Me 2 —(CH₂)₄-cHx H H H H7-2 H H Me 2 —(CH₂)₄-Ph H H H H 7-3 H H Me 2 —(CH₂)₅-cHx H H H H 7-4 H HMe 2 —(CH₂)₅-Ph H H H H 7-5 H H Me 2 —C≡C—(CH₂)₂-cHx H H H H 7-6 H H Me2 —C≡C—(CH₂)₂-Ph H H H H 7-7 H H Me 2 —C≡C—(CH₂)₃-cHx H H H H 7-8 H H Me2 —C≡C—(CH₂)₃-Ph H H H H 7-9 H H Me 2 —CO—(CH₂)₃-cHx H H H H 7-10 H H Me2 —CO—(CH₂)₃-Ph H H H H 7-11 H H Me 2 —CO—(CH₂)₄-cHx H H H H 7-12 H H Me2 —CO—(CH₂)₄-Ph H H H H

TABLE 8

Compd. R¹ R² R⁴ n —Y—Z—R⁵ R⁶ R⁷ R¹⁰ R¹¹ 8-1 H H Me 2 —(CH₂)₄-cHx H H H H8-2 H H Me 2 —(CH₂)₄-Ph H H H H 8-3 H H Me 2 —(CH₂)₅-cHx H H H H 8-4 H HMe 2 —(CH₂)₅-Ph H H H H 8-5 H H Me 2 —C≡C—(CH₂)₂-cHx H H H H 8-6 H H Me2 —C≡C—(CH₂)₂-Ph H H H H 8-7 H H Me 2 —C≡C—(CH₂)₃-cHx H H H H 8-8 H H Me2 —C≡C—(CH₂)₃-Ph H H H H 8-9 H H Me 2 —CO—(CH₂)₃-cHx H H H H 8-10 H H Me2 —CO—(CH₂)₃-Ph H H H H 8-11 H H Me 2 —CO—(CH₂)₄-cHx H H H H 8-12 H H Me2 —CO—(CH₂)₄-Ph H H H H

The exemplification compound numbers of preferred compounds havingformula (I) in the table 1 (formula (Ia-1), (Ia-2) and (Ia-3)), thetable 2 (formula (Ib-1), (Ib-2) and (1b-3), the table 3 (formula (1a-4)and the table 4 (formula (1a-5)) include:

1-21, from 1-30 to 1-46, from 1-93to 1-152, from 1-199 to 1-253, from1-263 to 1-272, from 1-283 to 1-298, from 1-345 to 1-401, from 1-411 to1-426, from 1-473 to 1-528, from 1-548 to 1-549, from 1-559 to 1-574,from 1-621 to 1-680, from 1-727 to 1-781, from 1-791 to 1-801, from1-831 to 1-836, from 1-896 to 1-949, from 1-959 to 1-974, from 1-1021 to1-1078, from 1-1081 to 1-1083, from 1-1093 to 1-1103, from 1-1113 to1-1127, from 1-1137 to 1-1152, from-1-1199 to 1-1255, from 1-1265 to1-1280, from 1-1327 to 1-1389, from 1-1399 to 1-1049, from 1-1419 to1-1430, 1-1433, from 1-1443 to 1-1445, from 1-1457 to 1-1466, from1-1484 to 1-1512, from 1-1531 to 1-1555, from1-1558 to 1-1565, from1-1584 to 1-1612, from 1-1630 to 1-1654, from 1-1657 to 1-1664, from1-1683 to 1-1729, from 1-1743 to 1-1949, from 2-1 to 2-10, from 2-28 to2-56, from 2-75 to 2-99, from 2-104 to 2-111, from 2-130 to 2-158, from2-176 to 2-200, from 2-203 to 2-210, from 2-229 to 2-281, and from 4-9to 4-12.

The exemplification compound numbers of the more preferred compoundsinclude 1-21, from 1-31 to 1-38, from 1-41 to 1-46, from 1-93 to 1-105,from 1-112 to 1-117, from 1-142 to 1-144, from 1-147 to 1-152, from1-199 to 1-211, from 1-248 to 1-250, 1-253, from 1-263 to 1-269, from1-284 to 1-289, from 1-293 to 1-298, from 1-345 to 1-357, from 1-364 to1-369, from 1-394 to 1-401, from 1-411 to 1-417, from 1-421to 1-426,from 1-474 to 1-485, from 1-492 to 1-497, from 1-522 to 1-528, 1-549,from 1-559 to 1-565 from 1-568 to 1-574, from 1-621 to 1-633, 1-640,1-643, from 1-670 to 1-672, from 1-676 to 1-680, from 1-727 to 1-739,from 1-776 to 1-778, 1-781, from 1-831 to 1-838, from 1-842 to 1-846,from 1-893 to 1-905, from 1-912 to 1-917, from 1-942 to 1-946, 1-949,from 1-959 to 1-965, from 1-970 to 1-974, from 1-1021 to 1-1033, from1-1040 to 1-1045, from 1-1070 to 1-1073, from 1-1081 to 1-1083, from1-1093 to 1-1099, 1-1103, from 1-1113 to 1-1119, from 1-1148 to 1-1152,from 1-1199 to 1-1211, from 1-1248 to 1-1252, from 1-1265 to 1-1271,from 1-1276 to 1-1280, from 1-1327 to 1-1339, from 1-1376 to 1-1380,1-1433, from 1-1443 to 1-1445, from 1-1459 to 1-1466, from 1-1484 to1-1499, from 1-1504 to 1-1512, from 1-1558 to 1-1565, from 1-1584 to1-1599, from 1-1604 to 1-1612, from 1-1630 to 1-1639, from 1-1657 to1-1658, from 1-1660 to 1-1664, from 1-1683 to 1-1692, from 1-1702 to1-1710, from 1-1743 to 1-1773, from 1-1796 to 1-1846, from 1-1848 to1-1876, from 1-1886 to 1-1904, from 2-3 to 2-10, from 2-28 to 2-37, from2-52 to 2-56, from 2-75 to 2-84, from 2-88 to 2-90, from 2-95 to 2-99,from 2-104 to 2-111, from 2-130 to 2-139, from 2-143 to 2-146, from2-150 to 2-158, from 2-176 to 2-185, from 2-189 to 2-191, from 2-196 to2-200, from 2-203 to 2-210, from 2-229 to 2-238, from 2-242 to 2-244,from 2-248 to 2-252, and from 4-9 to 4-12.

The exemplification compound numbers of the more preferred compoundsinclude 1-21, 1-42, from 1-93 to 1-105, from 1-112 to 1-117, from 1-142to 1-144, from 1-147 to 1-152, from 1-199 to 1-211, from 1-248 to 1-250,from 1-294 to 1-298, 1-351, 1-367, 1-411, 1-549, from 1-559 to 1-565,from 1-569 to 1-574, from 621 to 1-633, 1-643, from 1-670 to 1-672, from1-676 to 1-680, from 1-831 to 1-838, from 1-842 to 1-846, from 1-893 to1-905, from 1-912 to 1-917, from 1-942 to 1-944, 1-949, 1-1021, from1081 to 1-1083, from 1-1093 to 1-1099, 1-1462, from 1-1558 to 1-1565,from 1-1584 to 1-1599, from 1-1604 to 1-1612, from 1-1660 to 1664, from1-1707 to 1-1710, from 1762 to 1-1773, from 1816 to 1846, from 1-1848 to1-1859, from 1-1886 to 1-1904, and from 4-9 to 4-12.

The exemplification compound numbers of the still more preferredcompounds include

-   Exemplification compound number 1-93 having formula (Ia-1):    2-amino-2-methyl-4-[5-(5-phenylpentyl)furan-2-yl]butan-1-ol,-   Exemplification compound number 1-570 having formula (Ia-1):    2-amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]butan-1-ol,-   Exemplification compound number 1-621 having formula (Ia-1):    2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)furan-2-yl]butan-1-ol,-   Exemplification compound number 1-833 having formula (Ia-1):    2-amino-2-methyl-4-{5-[3-(4-methyl)phenoxyprop-1-ynyl]pyrrol-2-yl}butan-1-ol,-   Exemplification compound number 1-842 having formula (Ia-1):    2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]butan-1-ol,-   Exemplification compound number 1-1083 having formula (Ia-1):    2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)furan-2-yl]butan-1-ol,-   Exemplification compound number 1-1836 having formula (Ia-1):    2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]furan-2-yl}butan-1-ol,-   Exemplification compound number 1-628 having formula (Ia-1):    2-amino-2-methyl-4-{5-[5-(4-chlorophenyl)pent-1-ynyl]furan-2-yl}butan-1-ol,-   Exemplification compound number 1-640 having formula (Ia-1):    2-amino-2-methyl-4-{5-[5-(3-trifluoromethylphenyl)pent-1-ynyl]furan-2-yl}butan-1-ol,-   Exemplification compound number 1-835 having formula (Ia-1):    2-amino-2-methyl-4-{5-[3-(4-trifluoromethylphenoxy)prop-1-ynyl]furan-2-yl}butan-1-ol,-   Exemplification compound number 1-1831 having formula (Ia-1):    2-amino-2-methyl-4-{5-[3-(4-chlorophenoxy)prop-1-ynyl]furan-2-yl}butan-1-ol,-   Exemplification compound number 1-1838 having formula (Ia-1):    2-amino-2-methyl-4-{5-[3-(3-trifluoromethylphenoxy)prop-1-ynyl]furan-2-yl}butan-1-ol,-   Exemplification compound number 1-1842 having formula (Ia-1):    2-amino-2-methyl-4-{5-[3-(3,4-dimethoxylphenoxy)prop-1-ynyl]furan-2-yl}butan-1-ol,-   Exemplification compound number 1-621 having formula (Ia-2):    2-amino-2-methyl-4-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]butan-1-ol,-   Exemplification compound number 1-833 having formula (Ia-2):    2-amino-2-methyl-4-{1-methyl-5-[3-(4-methyl)phenoxyprop-1-ynyl]pyrrol-2-yl}butan-1-ol,-   Exemplification compound number 1-842 having formula (Ia-2):    2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylbut-1-ynyl)pyrrol-2-yl]butan-1-ol,-   Exemplification compound number 1-1836 having formula (Ia-2):    2-amino-2-methyl-4-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]pyrrol-2-yl}butan-1-ol,-   Exemplification compound number 1-93 having formula (Ia-2):    2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentyl)pyrrol-2-yl]butan-1-ol,-   Exemplification compound number 1-1093 having formula (Ia-2):    2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol,-   Exemplification compound number 1-1890 having formula (Ia-2):    2-amino-2-methyl-4-{1-methyl-5-[5-(4-chlorophenyl)pentanoyl]pyrrol-2-yl}butan-1-ol,-   Exemplification compound number 1-1896 having formula (Ia-2):    2-amino-2-methyl-4-{1-methyl-5-[5-(3-trifluoromethylphenyl)pentanoyl]pyrrol-2-yl}butan-1-ol,-   Exemplification compound number 1-1083 having formula (Ia-2):    2-amino-2-methyl-4-[1-methyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]butan-1-ol,-   Exemplification compound number 1-1082 having formula (Ia-2):    2-amino-2-methyl-4-[1-methyl-5-(4-phenylbutanoyl)pyrrol-2-yl]butan-1-ol,-   Exemplification compound number 1-1081 having formula (Ia-2):    2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]butan-1-ol,-   Exemplification compound number 4-12 having formula (Ia-5):    2-amino-2-methyl-4-[1-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol,-   Exemplification compound number 4-11 having formula (Ia-5):    2-amino-2-methyl-4-[1-ethyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]butan-1-ol,-   Exemplification compound number 4-10 having formula (Ia-5):    2-amino-2-methyl-4-[1-ethyl-5-(4-phenylbutanoyl)pyrrol-2-yl]butan-1-ol,-   Exemplification compound number 4-9 having formula (Ia-5):    2-amino-2-methyl-4-[1-ethyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]butan-1-ol,-   Exemplification compound number 1-21 having formula (Ia-3):    2-amino-2-methyl-4-[5-(4-cyclohexylbutyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-42 having formula (Ia-3):    2-amino-2-methyl-4-[5-(5-cyclohexylpentyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-93 having formula (Ia-3):    2-amino-2-methyl-4-[5-(5-phenylpentyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-294 having formula (Ia-3):    2-amino-2-methyl-4-[5-(4-cyclohexyloxybutyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-351 having formula (Ia-3):    2-amino-2-methyl-4-{5-[4-(4-fluorophenoxy)butyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-367 having formula (Ia-3):    2-amino-2-methyl-4-{5-[4-(4-methoxyphenoxy)butyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-473 having formula (Ia-3):    2-amino-2-methyl-4-[5-(4-benzyloxybutyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-549 having formula (Ia-3):    2-amino-2-methyl-4-[5-(4-cyclohexylbut-1-ynyl)    thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-559 having formula (Ia-3):    2-amino-2-methyl-4-[5-(4-phenylbut-1-ynyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-570 having formula (Ia-3):    2-amino-2-methyl-4-[5-(4-cyclohexylpent-1-ynyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-621 having formula (Ia-3):    2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-627 having formula (Ia-3):    2-amino-2-methyl-4-{5-[5-(4-fluorophenyl)pent-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-643 having formula (Ia-3):    2-amino-2-methyl-4-{5-[5-(4-methoxyphenyl)pent-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-833 having formula (Ia-3):    2-amino-2-methyl-4-{5-[3-(4-methylphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-834 having formula (Ia-3):    2-amino-2-methyl-4-{5-[3-(4-ethylphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-838 having formula (Ia-3):    2-amino-2-methyl-4-{5-[3-(4-methylthiophenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-842 having formula (Ia-3):    2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-899 having formula (Ia-3):    2-amino-2-methyl-4-{5-[4-(4-fluorophenoxy)but-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-903 having formula (Ia-3):    2-amino-2-methyl-4-{5-[4-(4-methylphenoxy)but-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-949 having formula (Ia-3):    2-amino-2-methyl-4-[5-(3-cyclohexylmethoxyprop-1-ynyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-1021 having formula (Ia-3):    2-amino-2-methyl-4-[5-(4-benzyloxybut-1-ynyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-1081 having formula (Ia-3):    2-amino-2-methyl-4-[5-(4-cyclohexylbutanoyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-1082 having formula (Ia-3):    2-amino-2-methyl-4-[5-(4-phenylbutanoyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-1083 having formula (Ia-3):    2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-1093 having formula (Ia-3):    2-amino-2-methyl-4-[5-(5-phenylpentanoyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-1094 having formula (Ia-3):    2-amino-2-methyl-4-{5-[5-(4-fluorophenyl)pentanoyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-1462 having formula (Ia-3):    2-amino-2-ethyl-4-[5-(5-cyclohexylpentyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-1561 having formula (Ia-3):    2-amino-2-ethyl-4-[5-(5-cyclohexylpent-1-ynyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-1707 having formula (Ia-3):    2-amino-2-ethyl-4-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-1831 having formula (Ia-3):    2-amino-2-methyl-4-{5-[3-(4-chlorophenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-1834 having formula (Ia-3):    2-amino-2-methyl-4-{5-[3-(3-methylphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-1836 having formula (Ia-3):    2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-1841 having formula (Ia-3):    2-amino-2-methyl-4-{5-[3-(3-methoxyphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-1842 having formula (Ia-3):    2-amino-2-methyl-4-{5-[3-(3,4-dimethoxyphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-1843 having formula (Ia-3):    2-amino-2-methyl-4-{5-[3-(3,5-dimethoxyphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-1845 having formula (Ia-3):    2-amino-2-methyl-4-{5-[3-(3-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,    and-   Exemplification compound number 1-1846having formula (Ia-3):    2-amino-2-methyl-4-{5-[3-(4-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol.

The exemplification compound numbers of particularly preferred compoundsinclude

-   Exemplification compound number 1-93 having formula (Ia-1):    2-amino-2-methyl-4-[5-(5-phenylpentyl)furan-2-yl]butan-1-ol,-   Exemplification compound number 1-570 having formula (Ia-1):    2-amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]butan-1-ol,-   Exemplification compound number 1-621 having formula (Ia-1):    2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)furan-2-yl]butan-1-ol,-   Exemplification compound number 1-842 having formula (Ia-1):    2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]butan-1-ol,-   Exemplification compound number 1-1083 having formula (Ia-1):    2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)furan-2-yl]butan-1-ol,-   Exemplification compound number 1-1836 having formula (Ia-1):    2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]furan-2-yl}butan-1-ol-   Exemplification compound number 1-621 having formula (Ia-2):    2-amino-2-methyl-4-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]butan-1-ol,-   Exemplification compound number 1-833 having formula (Ia-2):    2-amino-2-methyl-4-[1-methyl-5-[3-(4-methyl)phenoxyprop-1-ynyl]pyrrol-2-yl]butan-1-ol,-   Exemplification compound number 1-842 having formula (Ia-2):    2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexyloxybut-1-ynyl)pyrrol-2-yl]butan-1-ol,-   Exemplification compound number 1-1093 having formula (Ia-2):    2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol,-   Exemplification compound number 1-1836 having formula (Ia-2):    2-amino-2-methyl-4-[1-methyl-5-[3-(3,4-dimethyl)phenoxyprop-1-ynyl]pyrrol-2-yl]butan-1-ol,-   Exemplification compound number 1-1083 having formula (Ia-2):    2-amino-2-methyl-4-[1-methyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]butan-1-ol,-   Exemplification compound number 1-1082 having formula (Ia-2):    2-amino-2-methyl-4-[1-methyl-5-(4-phenylbutanoyl)pyrrol-2-yl]butan-1-ol,-   Exemplification compound number 1-1081 having formula (Ia-2):    2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]butan-1-ol,-   Exemplification compound number 4-12 having formula (Ia-5):    2-amino-2-methyl-4-[1-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol,-   Exemplification compound number 4-11 having formula (Ia-5):    2-amino-2-methyl-4-[1-ethyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]butan-1-ol,-   Exemplification compound number 4-10 having formula (Ia-5):    2-amino-2-methyl-4-[1-ethyl-5-(4-phenylbutanoyl)pyrrol-2-yl]butan-1-ol,-   Exemplification compound number 4-9 having formula (Ia-5):    2-amino-2-methyl-4-[1-ethyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]butan-1-ol,-   Exemplification compound number 1-21 having formula (Ia-3):    2-amino-2-methyl-4-[5-(4-cyclohexylbutyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-42 having formula (Ia-3):    2-amino-2-methyl-4-[5-(5-cyclohexylpentyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-93 having formula (Ia-3):    2-amino-2-methyl-4-[5-(5-phenylpentyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-294 having formula (Ia-3):    2-amino-2-methyl-4-[5-(4-cyclohexyloxybutyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-351 having formula (Ia-3):    2-amino-2-methyl-4-{5-[4-(4-fluorophenoxy)butyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-367 having formula (Ia-3):    2-amino-2-methyl-4-{5-[4-(4-methoxyphenoxy)butyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-473 having formula (Ia-3):    2-amino-2-methyl-4-[5-(4-benzyloxybutyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-549 having formula (Ia-3):    2-amino-2-methyl-4-[5-(4-cyclohexylbut-1-ynyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-559 having formula (Ia-3):    2-amino-2-methyl-4-[5-(4-phenylbut-1-ynyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-570 having formula (Ia-3):    2-amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-621 having formula (Ia-3):    2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-627 having formula (Ia-3):    2-amino-2-methyl-4-{5-[5-(4-fluorophenyl)pent-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-643 having formula (Ia-3):    2-amino-2-methyl-4-{5-[5-(4-methoxyphenyl)pent-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-833 having formula (Ia-3):    2-amino-2-methyl-4-{5-[3-(4-methylphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-834 having formula (Ia-3):    2-amino-2-methyl-4-{5-[3-(4-ethylphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-838 having formula (Ia-3):    2-amino-2-methyl-4-{5-[3-(4-methylthiophenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-842 having formula (Ia-3):    2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-899 having formula (Ia-3):    2-amino-2-methyl-4-{5-[4-(4-fluorophenoxy)but-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-903 having formula (Ia-3):    2-amino-2-methyl-4-{5-[4-(4-methylphenoxy)but-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-949 having formula (Ia-3):    2-amino-2-methyl-4-[5-(3-cyclohexylmethoxyprop-1-ynyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-1021 having formula (Ia-3):    2-amino-2-methyl-4-[5-(4-benzyloxybut-1-ynyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-1081 having formula (Ia-3):    2-amino-2-methyl-4-[5-(4-cyclohexylbutanoyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-1082 having formula (Ia-3):    2-amino-2-methyl-4-[5-(4-phenylbutanoyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-1083 having formula (Ia-3):    2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-1093 having formula (Ia-3):    2-amino-2-methyl-4-[5-(5-phenylpentanoyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-1094 having formula (Ia-3):    2-amino-2-methyl-4-{5-[5-(4-fluorophenyl)pentanoyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-1462 having formula (Ia-3):    2-amino-2-ethyl-4-[5-(5-cyclohexylpentyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-1561 having formula (Ia-3):    2-amino-2-ethyl-4-[5-(5-cyclohexylpent-1-ynyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-1707 having formula (Ia-3):    2-amino-2-ethyl-4-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]butan-1-ol,-   Exemplification compound number 1-1831 having formula (Ia-3):    2-amino-2-methyl-4-{5-[3-(4-chlorophenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-1834 having formula (Ia-3):    2-amino-2-methyl-4-{5-[3-(3-methylphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-1836 having formula (Ia-3):    2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-1841 having formula (Ia-3):    2-amino-2-methyl-4-{5-[3-(3-methoxyphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-1842 having formula (Ia-3):    2-amino-2-methyl-4-{5-[3-(3,4-dimethoxyphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-1843 having formula (Ia-3):    2-amino-2-methyl-4-{5-[3-(3,5-dimethoxyphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,-   Exemplification compound number 1-1845 having formula (Ia-3):    2-amino-2-methyl-4-{5-[3-(3-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,    and-   Exemplification compound number 1-1846 having formula (Ia-3):    2-amino-2-methyl-4-{5-[3-(4-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol.

The exemplification compound numbers of preferred compounds havingformula (II)in the table 5(formula (IIa-1), (IIa-2)and (IIa-3)), thetable 6 (formula (IIb-1), (IIb-2) and (IIb-3)), and the table 7 (formula(IIa-4))include:

-   5-19, from 5-23 to 5-32, from 5-36 to 5-45, from 5-49 to 5-58, from    5-62 to 5-71, from 5-75 to 5-84, from 5-88 to 5-102, from 5-106 to    5-156, from 5-160 to 5-214, from 5-218 to 5-268, from 5-272 to    5-321, from 5-325 to 5-334, from 5-338 to 5-347, from 5-351 to    5-360, from 5-364 to 5-373, from 5-377 to 5-386, from 5-390 to    5-404, from 5-408 to 5-458, from 5-462 to 5-513, from 5-517 to    5-526, from 5-530 to 5-544, from 5-548 to 5-598, from 5-602 to    5-657, 5-670, from 5-674 to 5-683, 5-696, from 5-700 to 5-717, from    5-721 to 5-730, from 5-734 to 5-743, from 5-747 to 5-756, from 5-760    to 5-774, from 5-778 to 5-828, from 5-832 to 5-886, from 5-890 to    5-940, from 5-944 to 5-993, from 5-997 to 5-1006, from 5-1010 to    5-1019, 5-1045, from 5-1049 to 5-1058, from 5-1062 to 5-1076, from    5-1080 to 5-1130, from 5-1134 to 5-1185, from 5-1189 to 5-1198, from    5-1202 to 5-1208, from 5-1212 to 5-1216, from 5-1220 to 5-1270, from    5-1274 to 5-1331, from 5-1335 to 5-1344, from 5-1348 to 5-1357, from    5-1361 to 5-1370, from 5-1374 to 5-1387, from 5-1391 to 5-1400, from    5-1404 to 5-1418, from 5-1422 to 5-1472, from 5-1476 to 5-1527, from    5-1531 to 5-1540, from 5-1544 to 5-1558, from 5-1562 to 5-1612, from    5-1616 to 5-1673, from 5-1677 to 5-1686, from 5-1690 to 1-1699, from    5-1703 to 5-1712, from 5-1716 to 5-1729, from 5-1733 to 5-1744, from    5-1748 to 5-1768, from 5-1772 to 5-1793, from 5-1797 to 5-1820, from    5-1824 to 5-1846, from 5-1850 to 5-1869, 5-1872, 5-1876, 5-1880,    5-1884, from 5-1888 to 5-1892, 5-1896, 5-1900, from5-1908 to 5-1913,    from 5-1917 to 5-1939, from 5-1943 to 5-1966, from 5-1970 to 5-1991,    from 5-1995 to 5-2013, 5-2017, 5-2021, 5-2025, 5-2029, 5-2033, from    5-2037 to 5-2042, from 5-2046 to 5-2068, from 5-2072 to 5-2089,    5-2093, 5-2097, 5-2101, 5-2105, 5-2109, 5-2113, 5-2117, 5-2121,    5-2125, 5-2129, 5-2133, 5-2135, from 5-2139 to 5-2158, from 5-2161    to 5-2164, from 5-2185 to 5-2346, from 5-2398 to 5-2557,-   from 6-9 to 6-18, from 6-22 to 6-43, from 6-47 to 6-70, from 6-74 to    6-96, from 6-100 to 6-119, 6-142, 6-146, 6-150, 6-154, from 6-158 to    6-163, from 6-167 to 6-183, from 6-185 to 6-189, from 6-193 to    6-216, from 6-220 to 6-241, from 6-245 to 6-263, 6-267, 6-271,    6-275, 6-279, 6-283, from 6-287 to 6-292, from 6-296 to 6-318, from    6-322 to 6-338, 6-343, 6-347, 6-351, 6-371, from 6-375 to 6-377,    from 6-381 to 6-407, from 6-416 to 6-511, and-   from 7-9 to 7-12.

The exemplification compound numbers of the more preferred compoundsinclude:

-   5-19, 5-32, from 5-36 to 5-45, 5-57, from 5-62 to 5-71, 5-84, 5-88,    from 5-97 to 5-100, from 5-152 to 5-154, from 5-160 to 5-214, from    5-218 to 5-227, from 5-264 to 5-268, from 5-272 to 5-321, 5-334,    5-347, 5-360, 5-373, 5-386, from 5-390 to 5-402, from 5-454 to    5-458, from 5-462 to 5-513, 5-526, from 5-530 to 5-542, from 5-594    to 5-598, from 5-602 to 5-653, 5-743, 5-756, from 5-760 to 5-768,    from 5-770 to 5-774, from 5-778 to 5-828, from 5-832 to 5-886, from    5-890 to 5-940, from 5-944 to 5-993, 5-1045, 5-1058, from 5-1062 to    5-1074, from 5-1126 to 5-1130, from 5-1134 to 5-1185, 5-1198, from    5-1202 to 5-1208, from 5-1212 to 5-1214, from 5-1266 to 5-1270, from    5-1274 to 5-1331, 5-1344, from 5-1348 to 5-1357, 5-1370, from 5-1374    to 5-1387, 5-1400, from 5-1404 to 5-1416, from 5-1468 to 5-1472,    from 5-1476 to 5-1527, 5-1540, from 5-1544 to 5-1556, from 5-1608 to    5-1612, from 5-1616 to 5-1666, 5-1729, 5-1742, 5-1744, from 5-1759    to 5-1767, from 5-1789 to 5-1793, from 5-1797 to 5-1818, from 5-1842    to 5-1846, 5-1900, from 5-1908 to 5-1913, from 5-1935 to 5-1939,    from 5-1943 to 5-1966, from 5-1987 to 5-1991, 5-2013, 5-2017,    5-2029, 5-2033, from 5-2037 to 5-2042, from 5-2064 to 5-2068, from    5-2072 to 5-2089, 5-2093, 5-2097, 5-2101, 5-2105, 5-2109, 5-2129,    5-2133, 5-2135, from 5-2185 to 5-2346, from 5-2398 to 5-2557, from    6-11 to 6-18, from 6-39 to 6-43, from 6-47 to 6-70, from 6-185 to    6-189, from 6-193 to 6-216, from 6-287 to 6-292, 6-338, 6-343,    6-347, 6-351, from 6-416 to 6-511, and from 7-9 to 7-12.

The exemplification compound numbers of the more preferred compoundsinclude:

-   5-45, 5-71, 5-84, 5-88, from 5-97 to 5-100, from 5-152 to 5-154,    from 5-160 to 5-206, from 5-209 to 5-212, from 5-264 to 5-266,    5-334, 5-373, 5-386, from 5-390 to 5-402, from 5-454 to 5-458, from    5-462 to 5-485, 5-509, 5-510, 5-513, 5-526, from 5-530 to 5-542,    from 5-594 to 5-598, from 5-602 to 5-613, 5-649, 5-650, 5-743,    5-756, from 5-760 to 5-768, from 5-770 to 5-772, from 5-824 to    5-828, from 5-832 to 5-884, 5-936, 5-1045, 5-1058, from 5-1062 to    5-1074, from 5-1126 to 5-1130, from 5-1134 to 5-1145, from 5-1148 to    5-1151, 5-1162, 5-1163, from 5-1179 to 5-1182, 5-1185, 5-1198, from    5-1202 to 5-1208, 5-1212, 5-1213, 5-1214, from 5-1266 to 5-1270,    from 5-1274 to5-1285, from 5-1288 to 5-1291, from 5-1319 to 5-1322,    from 5-1329 to 5-1331, 5-1344, from 5-1348 to 5-1357, 5-1370,    5-1387, 5-1400, from 5-1404 to 5-1416, from 5-1468 to 5-1472, from    5-1476 to 5-1487, from 5-1490 to 5-1493, 5-1504, 5-1505, from 5-1521    to 5-1524, 5-1527, 5-1540, from 5-1544 to 5-1556, from 5-1608 to    5-1612, from 5-1616 to 5-1627, 5-1663, 5-1664, 5-1729, 5-1742,    5-1744, from 5-1761 to 5-1766, from 5-1789 to 5-1791, from 5-1815 to    5-1818, 5-1900, 5-1909, 5-1962, from 5-2064 to 5-2066, 5-2089,    5-2093, 5-2097, 5-2101, 5-2105, 5-2133, from 5-2216 to 5-2288, from    5-2290 to 5-2346, from 5-2398 to 5-2557, and from 7-9 to 7-12.

The exemplification compound numbers of the still more preferredcompounds include:

-   Exemplification compound number 5-84 having formula (IIa-1): mono    2-amino-2-methyl-4-[5-(5-phenylpentyl)furan-2-yl]-1-butyl phosphate,-   Exemplification compound number 5-770 having formula (IIa-1): mono    2-amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-824 having formula (IIa-1): mono    2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)furan-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1063 having formula (IIa-1): mono    2-amino-2-methyl-4-{5-[3-(4-methylphenoxyl)prop-1-ynyl]furan-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1072 having formula (IIa-1): mono    2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1331 having formula (IIa-1): mono    2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)furan -2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-2278 having formula (IIa-1): mono    2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop    -1-ynyl]furan-2-yl}-1-butyl phosphate,-   Exemplification compound number 5-834 having formula (IIa-1): mono    2-amino-2-methyl-4-{5-[5-(4-chlorophenyl)pent-1-ynyl]furan-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-846 having formula (IIa-1): mono    2-amino-2-methyl-4-{5-[5-(3-trifluoromethylphenyl)pent-1-ynyl]furan-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1065 having formula (IIa-1): mono    2-amino-2-methyl-4-{5-[3-(4-trifluoromethylphenoxyl)prop-1-ynyl]furan-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2273 having formula (IIa-1): mono    2-amino-2-methyl-4-{5-[3-(4-chlorophenoxyl)prop-1-ynyl]furan-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2280 having formula (IIa-1): mono    2-amino-2-methyl-4-{5-[3-(3-trifluoromethylphenoxyl)prop-1-ynyl]furan-2-yl)}-1-butyl    phosphate,-   Exemplification compound number 5-2284 having formula (IIa-1): mono    2-amino-2-methyl-4-{5-[3-(3,4-dimethoxyphenoxy)prop    -1-ynyl]furan-2-yl}-1-butyl phosphate,-   Exemplification compound number 5-824 having formula (IIa-2): mono    2-amino-2-methyl-4-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1063 having formula (IIa-2): mono    2-amino-2-methyl-4-{1-methyl-5-[3-(4-methyl)phenoxyprop-1-ynyl]pyrrol-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1072 having formula (IIa-2): mono    2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexyloxybut-1-ynyl)pyrrol-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-2278 having formula (IIa-2): mono    2-amino-2-methyl-4-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]pyrrol-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-84 having formula (IIa-2): mono    2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentyl)pyrrol-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1344 having formula (IIa-2): mono    2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-2332 having formula (IIa-2): mono    2-amino-2-methyl-4-{1-methyl-5-[5-(4-chlorophenyl)pentanoyl]pyrrol-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2338 having formula (IIa-2): mono    2-amino-2-methyl-4-{1-methyl-5-[5-(3-trifluoromethylphenyl)pentanoyl]pyrrol-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1331 having formula (IIa-2): mono    2-amino-2-methyl-4-[1-methyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1330 having formula (IIa-2): mono    2-amino-2-methyl-4-[1-methyl-5-(4-phenylbutanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1329 having formula (IIa-2): mono    2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   Exemplification compound number 7-12 having formula (IIa-4): mono    2-amino-2-methyl-4-[1-ethyl-5-(5-phenylpentanoyl)pyrrol    -2-yl]-1-butyl phosphate,-   Exemplification compound number 7-11 having formula (IIa-4): mono    2-amino-2-methyl-4-[1-ethyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   Exemplification compound number 7-10 having formula (IIa-4): mono    2-amino-2-methyl-4-[1-ethyl-5-(4-phenylbutanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   Exemplification compound number 7-9 having formula (IIa-4): mono    2-amino-2-methyl-4-[1-ethyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-71 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-cyclohexylbutyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-84 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-phenylbutyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-98 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(5-cyclohexylpentyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-152 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(5-phenylpentyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-210 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(6-cyclohexylhexyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-264 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(6-phenylhexyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-373 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(3-cyclohexyloxypropyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-386 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(3-phenoxypropyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-400 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-cyclohexyloxybutyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-454 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-phenoxylbutyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-509 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(5-cyclohexyloxypentyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-510having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(5-phenoxypentyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-513 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(3-cyclohexylmethoxypropyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-743 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-cyclohexylbut-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-756 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-phenylbut-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-770 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)thiophen    -2-yl]-1-butyl phosphate,-   Exemplification compound number 5-824 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-882 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(6-cyclohexylhex-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-936 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(6-phenylhex-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1045 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(3-cyclohexyloxyprop-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1058having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(3-phenoxyprop-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1072 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1126having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-phenoxybut-1-ynyl)thiophen -2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1181 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(5-cyclohexyloxypent-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1182 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(5-phenoxypent-1-ynyl)thiophen-2-yl]-¹-butyl    phosphate,-   Exemplification compound number 5-1185 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(3-cyclohexylmethoxyprop-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1329 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-cyclohexylbutanoyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1330 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-phenylbutanoyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1331 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1344 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(5-phenylpentanoyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1357 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(6-cyclohexylhexanoyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1370 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(6-phenylhexanoyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1387 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(3-cyclohexyloxypropanoyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1400 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(3-phenoxypropanoyl)thiophen -2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1414 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-cyclohexyloxybutanoyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1468 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-phenoxybutanoyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1523 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(5-cyclohexyloxypentanoyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1524 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(5-phenoxypentanoyl)thiophen -2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1527 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(3-cyclohexylmethoxypropanoyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1729 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-cyclohexylmethoxyphenyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1742 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-cyclohexylethoxyphenyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1744 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-benzyloxyphenyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1761 having formula (IIa-3): mono    2-amino-2-ethyl-4-[5-(4-cyclohexylbutyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1764 having formula (IIa-3): mono    2-amino-2-ethyl-4-[5-(5-cyclohexylpentyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1816 having formula (IIa-3): mono    2-amino-2-ethyl-4-[5-(6-cyclohexylhexyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1900 having formula (IIa-3): mono    2-amino-2-ethyl-4-[5-(4-cyclohexylbut-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1909 having formula (IIa-3): mono    2-amino-2-ethyl-4-[5-(5-cyclohexylpent-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1962 having formula (IIa-3): mono    2-amino-2-ethyl-4-[5-(6-cyclohexylhex-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-2089 having formula (IIa-3): mono    2-amino-2-ethyl-4-[5-(4-cyclohexylbutanoyl)thiophen -2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-2097 having formula (IIa-3): mono    2-amino-2-ethyl-4-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]-1-butylphosphate,    and-   Exemplification compound number 5-2105 having formula (IIa-3): mono    2-amino-2-ethyl-4-[5-(6-cyclohexylhexanoyl)thiophen -2-yl]-1-butyl    phosphate, and-   Exemplification compound number 5-463 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-fluorophenoxy)butyl]thiophen    -2-yl}-1-butyl phosphate,-   Exemplification compound number 5-479 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-methoxyphenoxy)butyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-594 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-benzyloxybutyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-760 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-fluorophenyl)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-761 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-methylphenyl)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-762 having formula (IIa-3) mono    2-amino-2-methyl-4-{5-[4-(4-ethylphenyl)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-763 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-trifluoromethylphenyl)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-764 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-methoxyphenyl)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-765 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-ethoxyphenyl)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-766 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-methylthiophenyl)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-832 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3-fluorophenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-833 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(4-fluorophenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-834 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(4-chlorophenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-836 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3-methylphenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-837 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(4-methylphenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-846 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3-trifluoromethylphenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-847 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(4-trifluorophenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-848 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3-methoxyphenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-849 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(4-methoxyphenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-860 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3-methylthiophenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-861 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(4-methylthiophenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-877 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3,4-dimethylphenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-878 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3,5-dimethylphenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1050 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(4-methylcyclohexyloxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1062 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(4-fluorophenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1063 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(4-methylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1064 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(4-ethylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1065 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(4-trifluoromethylphenoxyl)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1066 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(4-methoxyphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1067 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(4-ethoxyphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1068 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(4-methylthiophenoxy)prop    -1-ynyl]thiophen-2-yl}-1-butyl phosphate,-   Exemplification compound number 5-1134 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3-fluorophenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1135 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-fluorophenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1136 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-chlorophenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1138 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3-methylphenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1139 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-methylphenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1148 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3-trifluoromethylphenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1149 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-trifluoromethylphenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1150 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3-methoxyphenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1151 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-methoxyphenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1162 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3-methylthiophenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1163 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-methylthiophenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1179 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3,4-dimethylphenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1180 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3,5-dimethylphenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1198 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(3-benzyloxyprop-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1202 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(4-fluorophenyl)methoxyprop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1203 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(4-methylphenyl)methoxyprop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1204 having formula (IIa-3):    mono2-amino-2-methyl-4-{5-[3-(4-ethylphenyl)methoxyprop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1205 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(4-trifluoromethylphenyl)methoxyprop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1206 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(4-methoxyphenyl)methoxyprop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1207 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(4-ethoxyphenyl)methoxyprop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1208 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(4-methylthiophenyl)methoxyprop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1212 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-cyclohexylmethoxybut-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1266 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-benzyloxybut-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1274 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3-fluorophenyl)methoxybut-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1275 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-fluorophenyl)methoxybut-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1276 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-chlorophenyl)methoxybut-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1278 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3-methylphenyl)methoxybut-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1279 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-methylphenyl)methoxybut-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1288-having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3-trifluoromethylphenyl)methoxybut-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1289 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-trifluoromethylphenyl)methoxybut-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1290 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3-methoxyphenyl)methoxybut-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1291 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-methoxyphenyl)methoxybut-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1319 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3,4-dimethylphenyl)methoxybut-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1320 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3,5-dimethylphenyl)methoxybut-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1348 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(4-fluorophenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1349 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(4-methylphenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1350 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(4-ethylphenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1351 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(4-trifluoromethylphenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1352 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(4-methoxyphenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1353 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(4-ethoxyphenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1354 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(4-methylthiophenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1476 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3fluorophenoxy)butanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1477 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-fluorophenoxy)butanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1478 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-chlorophenoxy)butanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1480 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3-methylphenoxy)butanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1481 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-methylphenoxy)butanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1490 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3-trifluoromethylphenoxy)butanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1491 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-trifluoromethylphenoxy)butanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1492 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3-methoxyphenoxy)butanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1493 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-methoxyphenoxy)butanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1504 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3-methylthiophenoxy)butanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1505 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-methylthiophenoxy)butanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1521 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3,4-dimethylphenoxy)butanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1522 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3,5-dimethylphenoxy)butanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2093 having formula (IIa-3): mono    2-amino-2-ethyl-4-[5-(4-phenylbutanoyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-2101 having formula (IIa-3): mono    2-amino-2-ethyl-4-[5-(5-phenylpentanoyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-2109 having formula (IIa-3): mono    2-amino-2-ethyl-4-[5-(6-phenylhexanoyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-2257 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3,4-difluorophenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2258 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3,5-difluorophenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2259 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3-chlorophenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2260 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3,4-dichlorophenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2261 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3,5-dichlorophenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2262 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3,4-ditrifluoromethylphenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2263 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3,5-ditrifluoromethylphenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2264 having formula(IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3,4-dimethoxyphenyl)pent    -1-ynyl]thiophen-2-yl}-1-butyl phosphate,-   Exemplification compound number 5-2265 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3,5-dimethoxyphenyl)pent    -1-ynyl]thiophen-2-yl}-1-butyl phosphate,-   Exemplification compound number 5-2266 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3,4,5-trimethoxyphenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2267 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3-acetylphenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2268 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(4-acetylphenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2269 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(3-fluorophenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2270 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(3,4-difluorophenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2271 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(3,5-difluorophenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2272 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(3-chlorophenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2273 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(4-chlorophenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2274 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(3,4-dichlorophenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2275 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(3,5-dichlorophenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2276 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(3-methylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2278 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2279 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(3,5-dimethylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2280 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(3-trifluoromethylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2281 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(3,4-ditrifluoromethylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2282 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(3,5-ditrifluoromethylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2283 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(3-methoxyphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2284 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(3,4-dimethoxyphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2285 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(3,5-dimethoxyphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2286 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(3,4,5-trimethoxyphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2287 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(3-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2288 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(4-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2290 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3,4-difluorophenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2291 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3,5-difluorophenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2292 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3-chlorophenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2293 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3,4-dichlorophenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2294 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3,5-dichlorophenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2295 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3,4-di(trifluoromethyl)phenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2296 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3,5-di(trifluoromethyl)phenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2297 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3,4-dimethoxyphenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2298 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3,5-dimethoxyphenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2299 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(3,4,5-trimethoxyphenoxy)but-1-ynyl]thiophen-2-yl)-1-butyl    phosphate,-   Exemplification compound number 5-2300 having formula (IIa-3): mono    2-amino-2-methyl-4-15-[4-(3-acetylphenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2301 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-acetylphenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2328 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3-fluorophenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2329 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3,4-difluorophenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2330 having formula (IIa-3):    mono2-amino-2-methyl-4-{5-[5-(3,5-difluorophenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2331 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3-chlorophenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2332 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(4-chlorophenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2333 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3,4-dichlorophenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2334 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3,5-dichlorophenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2335 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3-methylphenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2336 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3,4-dimethylphenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2337 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3,5-dimethylphenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2338 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3-trifluoromethylphenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2339 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3,4-ditrifluoromethylphenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2340 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3,5-ditrifluoromethylphenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2341 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3-methoxyphenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2342 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3,4-dimethoxyphenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2343 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3,5-dimethoxyphenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2344 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3,4,5-trimethoxyphenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2345 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(3-acetylphenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate, and-   Exemplification compound number 5-2346 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(4-acetylphenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate.

The exemplification compound numbers of the most preferred compoundsinclude:

-   Exemplification compound number 5-84 having formula (IIa-1): mono    2-amino-2-methyl-4-[5-(5-phenylpentyl)furan-2-yl]-1-butyl phosphate,-   Exemplification compound number 5-770 having formula (IIa-1): mono    2-amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-824 having formula (IIa-1): mono    2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)furan-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1072 having formula (IIa-1): mono    2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1331 having formula (IIa-1): mono    2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)furan-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-2278 having formula (IIa-1): mono    2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]furan-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-824 having formula (IIa-2): mono    2-amino-2-methyl-4-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1063 having formula (IIa-2): mono    2-amino-2-methyl-4-{1-methyl-5-[3-(4-methyl)phenoxyprop-1-ynyl]pyrrol-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1072 having formula (IIa-2): mono    2-amino-2-methyl-⁴-[1-methyl-5-(4-cyclohexyloxybut-1-ynyl)pyrrol-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-2278 having formula (IIa-2): mono    2-amino-2-methyl-4-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]pyrrol-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1344 having formula (IIa-2): mono    2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1331 having formula (IIa-2): mono    2-amino-2-methyl-4-[1-methyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1330 having formula (IIa-2): mono    2-amino-2-methyl-4-[1-methyl-5-(4-phenylbutanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1329 having formula (IIa-2): mono    2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   Exemplification compound number 7-12 having formula (IIa-4): mono    2-amino-2-methyl-4-[1-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   Exemplification compound number 7-11 having formula (IIa-4): mono    2-amino-2-methyl-4-[1-ethyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   Exemplification compound number 7-10 having formula (IIa-4): mono    2-amino-2-methyl-4-[1-ethyl-5-(4-phenylbutanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   Exemplification compound number 7-9 having formula (IIa-4): mono    2-amino-2-methyl-4-[1-ethyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-71 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-cyclohexylbutyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-98 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(5-cyclohexylpentyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-152 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(5-phenylpentyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-400 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-cyclohexyloxybutyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-463 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-fluorophenoxy)butyl]thiophne-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-479 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-methoxyphenoxy)butyl]thiophne-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-594 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-benzyloxybutyl)thiophne-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-743 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-cyclohexylbut-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-756 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-phenylbut-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-770 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-824 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-833 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(4-fluorophenyl)pent-1-ynyl]thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-849 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(4-methoxyphenyl)pent-1-ynyl]thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1050 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(4-methylcyclohexyloxy)prop-1-ynyl]thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1063 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(4-methylphenoxy)prop-1-ynyl]thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1064 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(4-ethylphenoxy)prop-1-ynyl]thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1068 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(4-methylthiophenoxy)prop-1-ynyl]thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1072 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1135 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-fluorophenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1139 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[4-(4-methylphenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1185 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(3-cyclohexylmethoxyprop-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1266 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-benzyloxybut-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1329 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4cyclohexylbutanoyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1330 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(4-phenylbutanoyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1331 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1344 having formula (IIa-3): mono    2-amino-2-methyl-4-[5-(5-phenylpentanoyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1348 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[5-(4-fluorophenyl)pentanoyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-1764 having formula (IIa-3): mono    2-amino-2-ethyl-4-[5-(5-cyclohexylpentyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-1909 having formula (IIa-3): mono    2-amino-2-ethyl-4-[5-(5-cyclohexylpent-1-ynyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-2097 having formula (IIa-3): mono    2-amino-2-ethyl-4-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]-1-butyl    phosphate,-   Exemplification compound number 5-2273 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(4-chlorophenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2276 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(3-methylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2278 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2283 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(3-methoxyphenoxyl)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2284 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(3,4-dimethoxyphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2285 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(3,5-dimethoxyphenoxyl)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate,-   Exemplification compound number 5-2287 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(3-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate, and-   Exemplification compound number 5-2288 having formula (IIa-3): mono    2-amino-2-methyl-4-{5-[3-(4-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl    phosphate.

The exemplification compound numbers of preferred compounds havingformula (III) in the table 5 (formula (IIIa-1), (IIIa-2) and (IIIa-3)),the table 6 (formula (IIIb-1), (IIIb-2) and (IIIb-3), and the table 8(formula (IIIa-4)) include:

-   5-19, from 5-23 to 5-32, from 5-36 to 5-45, from 5-49 to 5-58, from    5-62 to 5-71, from 5-75 to 5-84, from 5-88 to 5-102, from 5-106 to    5-156, from 5-160 to 5-214, from 5-218 to 5-268, from 5-272 to    5-321, from 5-325 to 5-334, from5-338 to 5-347, from 5-351 to 5-360,    from 5-364 to 5-373, from 5-377 to 5-386, from 5-390 to 5-404, from    5-408 to 5-458, from 5-462 to 5-513, from 5-517 to 5-526, from 5-530    to 5-544, from 5-548 to 5-598, from 5-602 to 5-657, 5-670, from    5-674 to 5-683, 5-696, from 5-700 to 5-717, from 5-721 to 5-730,    from 5-734 to 5-743, from 5-747 to 5-756, from 5-760 to 5-774, from    5-778 to 5-828, from 5-832 to 5-886, from 5-890 to 5-940, from 5-944    to 5-993, from 5-997 to 5-1006, from 5-1010 to 5-1019, 5-1045, from    5-1049 to 5-1058, from 5-1062 to 5-1076, from 5-1080 to 5-1130, from    5-1134 to 5-1185, from 5-1189 to 5-1198, from 5-1202 to 5-1208, from    5-1212 to 5-1216, from 5-1220 to 5-1270, from 5-1274 to 5-1331, from    5-1335 to 5-1344, from 5-1348 to 5-1357, from 5-1361 to 5-1370, from    5-1374 to 5-1387, from 5-1391 to 5-1400, from 5-1404 to 5-1418, from    5-1422 to 5-1472, from 5-1476 to 5-1527, from 5-1531 to 5-1540, from    5-1544 to 5-1558, from 5-1562 to 5-1612, from 5-1616 to 5-1673, from    5-1677 to 5-1686, from 5-1690 to 1-1699, from 5-1703 to 5-1712, from    5-1716 to 5-1729, from5-1733 to 5-1744, from 5-1748 to 5-1768, from    5-1772 to 5-1793, from 5-1797 to 5-1820, from 5-1824 to 5-1846, from    5-1850 to 5-1869, 5-1872, 5-1876, 5-1880, 5-1884, from 5-1888 to    5-1892, 5-1896, 5-1900, from 5-1908 to 5-1913, from 5-1917 to    5-1939, from 5-1943 to 5-1966, from 5-1970 to 5-1991, from 5-1995 to    5-2013, 5-2017, 5-2021, 5-2025, 5-2029, 5-2033, from 5-2037 to    5-2042, from 5-2046 to 5-2068, from 5-2072 to 5-2089, 5-2093,    5-2097, 5-2101, 5-2105, 5-2109, 5-2113, 5-2117, 5-2121, 5-2125,    5-2129, 5-2133, 5-2135, from 5-2139 to 5-2158, from 5-2161 to    5-2164, from 5-2185 to 5-2346, from 5-2398 to 5-2557, from 6-9 to    6-18, from 6-22 to 6-43, from 6-47 to 6-70 from 6-74 to 6-96, from    6-100 to 6-119, 6-142, 6-146, 6-150, 6-154, from 6-158 to 6-163,    from 6-167 to 6-183, from 6-185 to 6-189, from 6-193 to 6-216, from    6-220 to6-241, from 6-245 to 6-263, 6-267, 6-271, 6-275, 6-279,    6-283, from 6-287 to 6-292, from 6-296 to 6-318, from 6-322 to    6-338, 6-343, 6-347, 6-351, 6-371, from 6-375 to 6-377, from 6-381    to 6-407, from 6-416 to 6-511, and from 8-9 to 8-12.

The exemplification compound numbers of the more preferred compoundsinclude:

-   5-19, 5-32, from 5-36 to 5-45, 5-57, from 5-62 to 5-71, 5-84, 5-88 ,    from 5-97 to 5-100, from 5-152 to 5-154, from 5-160 to 5-214, from    5-218to 5-227, from 5-264 to 5-268, from 5-272 to 5-321, 5-334,    5-347, 5-360,%5-373, 5-386, from 5-390 to 5-402, from 5-454 to    5-458, from 5-462 to 5-513, 5-526, from 5-530 to 5-542, from 5-594    to 5-598, from 5-602 to 5-653, 5-743, 5-756, from 5-760 to 5-768,    from 5-770 to 5-774, from 5-778 to 5-828, from 5-832 to 5-886, from    5-890 to 5-940, from 5-944 to 5-993, 5-1045, 5-1058, from 5-1062 to    5-1074, from 5-1126 to 5-1130, from 5-1134 to 5-1185, 5-1198, from    5-1202 to 5-1208, from 5-1212 to 5-1214, from 5-1266 to 5-1270, from    5-1274 to 5-1331, 5-1344, from 5-1348 to 5-1357, 5-1370, from 5-1374    to 5-1387, 5-1400, from 5-1404 to 5-1416, from 5-1468 to 5-1472,    from 5-1476 to 5-1527, 5-1540, from 5-1544 to 5-1556, from 5-1608 to    5-1612, from 5-1616 to 5-1666, 5-1729, 5-1742, 5-1744, from 5-1759    to 5-1767, from 5-1789 to 5-1793, from 5-1797 to 5-1818, from 5-1842    to 5-1846, 5-1900, from 5-1908 to 5-1913, from 5-1935 to 5-1939,    from 5-1943 to 5-1966, from 5-1987 to 5-1991, 5-2013, 5-2017,    5-2029, 5-2033, from 5-2037 to 5-2042, from 5-2064 to 5-2068, from    5-2072 to 5-2089, 5-2093, 5-2097, 5-2101, 5-2105, 5-2109, 5-2129,    5-2133, 5-2135, from 5-2185 to 5-2346, from 5-2398 to 5-2557,-   from 6-11 to 6-18, from 6-39 to 6-43, from 6-47 to 6-70, from 6-185    to 6-189, from 6-193 to 6-216, from 6-287 to 6-292, 6-338, 6-343,    6-347, 6-351, from 6-416 to 6-511, and from 8-9 to 8-12.

The exemplification compound numbers of the more preferred compoundsinclude:

-   5-45, 5-71, 5-84, 5-88, from 5-97 to 5-100, from 5-152 to 5-154,    from 5-160 to 5-206, from 5-209 to 5-212, from 5-264 to 5-266,    5-334, 5-373, 5-386, from 5-390 to 5-402, from 5-454 to 5-458, from    5-462 to 5-485, 5-509, 5-510, 5-513, 5-526, from 5-530 to 5-542,    from 5-594 to 5-598, from 5-602 to 5-613, 5-649, 5-650, 5-743,    5-756, from 5-760 to 5-768, from 5-770 to 5-772, from 5-824 to    5-828, from 5-832 to 5-884, 5-936, 5-1045, 5-1058, from 5-1062 to    5-1074, from 5-1126 to 5-1130, from 5-1134 to 5-1145, from 5-1148 to    5-1151, 5-1162, 5-1163, from 5-1179 to 5-1182, 5-1185, 5-1198, from    5-1202 to 5-1208, 5-1212, 5-1213, 5-1214, from 5-1266 to 5-1270,    from 5-1274 to 5-1285, from 5-1288 to 5-1291, from 5-1319 to 5-1322,    from 5-1329 to 5-1331, 5-1344, from 5-1348 to5-1357, 5-1370, 5-1387,    5-1400, from 5-1404 to 5-1416, from 5-1468 to 5-1472, from 5-1476 to    5-1487, from 5-1490 to 5-1493, 5-1504, 5-1505, from 5-1521 to    5-1524, 5-1527, 5-1540, from 5-1544 to 5-1556, from 5-1608 to    5-1612, from 5-1616 to 5-1627, 5-1663, 5-1664, 5-1729, 5-1742,    5-1744, from 5-1761 to 5-1766, from 5-1789 to 5-1791, from 5-1815 to    5-1818, 5-1900, 5-1909, 5-1962, from 5-2064 to 5-2066, 5-2089,    5-2093, 5-2097, 5-2105, 5-2133, from 5-2216 to 5-2288, from 5-2290    to 5-2346, from 5-2398 to 5-2557, and-   from 8-9 to 8-12.

The exemplification compound numbers of the still more preferredcompounds include:

-   Exemplification compound number 5-84 having formula (IIIa-1):    3-amino-3-methyl-5-[5-(5-phenylpentyl)furan-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-770 having formula (IIIa-1):    3-amino-3-methyl-5-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-824 having formula (IIIa-1):    3-amino-3-methyl-5-[5-(5-phenylpent-1-ynyl)furan-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1063 having formula (IIIa-1):    3-amino    -3-methyl-5-{5-[3-(4-methylphenoxy)prop-1-ynyl]furan-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-1072 having formula (IIIa-1):    3-amino-3-methyl-5-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1331 having formula (IIIa-1):    3-amino-3-methyl-5-[5-(5-cyclohexylpentanoyl)furan-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-2278 having formula (IIIa-1):    3-amino-3-methyl-5-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]furan-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-834 having formula (IIIa-1):    3-amino-3-methyl-5-{5-[5-(4-chlorophenyl)pent-1-ynyl]furan-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-846 having formula (IIIa-1):    3-amino-3-methyl-5-{5-[5-(3-trifluoromethylphenyl)pent-1-ynyl]furan-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-1065 having formula (IIIa-1):    3-amino-3-methyl-5-{5-[3-(4-trifluoromethylphenoxy)prop-1-ynyl]furan-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-2273 having formula (IIIa-1):    3-amino-3-methyl-5-{5-[3-(4-chlorophenoxy)prop-1-ynyl]furan-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-2280 having formula (IIIa-1):    3-amino-3-methyl-5-{5-[3-(3-trifluoromethylphenoxy)prop-1-ynyl]furan-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-2284 having formula (IIIa-1):    3-amino-3-methyl-5-{5-[3-(3,4-dimethoxyphenoxy)prop-1-ynyl]furan-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-824 having formula (IIIa-2):    3-amino-3-methyl-5-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1063 having formula (IIIa-2):    3-amino-3-methyl-5-{1-methyl-5-[3-(4-methyl)phenoxyprop-1-ynyl]pyrrol-2-yl)}pentylphosphonic    acid,-   Exemplification compound number 5-1072 having formula (IIIa-2):    3-amino-3-methyl-5-[1-methyl-5-(4-cyclohexyloxybut-1-ynyl)pyrrol-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-2278 having formula (IIIa-2):    3-amino-3-methyl-5-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]pyrrol-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-84 having formula (IIIa-2):    3-amino-3-methyl-5-[1-methyl-5-(5-phenylpentyl)pyrrol-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1344 having formula (IIIa-2):    3-amino-3-methyl-5-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-2332 having formula (IIIa-2):    3-amino-3-methyl-5-{1-methyl-5-[5-(4-chlorophenyl)pentanoyl]pyrrol-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-2338 having formula (IIIa-2):    3-amino-3-methyl-5-{1-methyl-5-[5-(3-trifluoromethylphenyl)pentanoyl]pyrrol-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-1331 having formula (IIIa-2):    3-amino-3-methyl-5-[1-methyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1330 having formula (IIIa-2):    3-amino-3-methyl-5-[1-methyl-5-(4-phenylbutanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1329 having formula (IIIa-2):    3-amino-3-methyl-5-[1-methyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   Exemplification compound number 8-12 having formula (IIIa-4):    3-amino-3-methyl-5-[1-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   Exemplification compound number 8-11 having formula (IIIa-4):    3-amino-3-methyl-5-[1-ethyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   Exemplification compound number 8-10 having formula (IIIa-4):    3-amino-3-methyl-5-[1-ethyl-5-(4-phenylbutanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   Exemplification compound number 8-9 having formula (IIIa-4):    3-amino-3-methyl-5-[1-ethyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-71 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(4-cyclohexylbutyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-84 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(4-phenylbutyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-98 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(5-cyclohexylpentyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-152 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(5-phenylpentyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-210 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(6-cyclohexylhexyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-264 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(6-phenylhexyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-373 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(3-cyclohexyloxypropyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-386 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(3-phenoxypropyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-400 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(4-cyclohexyloxybutyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-454 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(4-phenoxybutyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-509 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(5-cyclohexyloxypentyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-510 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(5-phenoxypentyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-513 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(3-cyclohexylmethoxypropyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1329 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(4-cyclohexylbutanoyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1330 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(4-phenylbutanoyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1331 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1344 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(5-phenylpentanoyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1357 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(6-cyclohexylhexanoyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1370 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(6-phenylhexanoyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1387 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(3-cyclohexyloxypropanoyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1400 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(3-phenoxypropanoyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1414 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(4-cyclohexyloxybutanoyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1468 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(4-phenoxybutanoyl)thiophen-72-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1523 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(5-cyclohexyloxypentanoyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1524 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(5-phenoxypentanoyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1527 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(3-cyclohexylmethoxypropanoyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1729 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(4-cyclohexylmethoxyphenyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1742 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(4-cyclohexylethoxyphenyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1744 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(4-benzyloxyphenyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1761 having formula (IIIa-3):    3-amino-3-ethyl-5-[5-(4-cyclohexylbutyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1764 having formula (IIIa-3):    3-amino-3-ethyl-5-[5-(5-cyclohexylpentyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1816 having formula (IIIa-3):    3-amino-3-ethyl-5-[5-(6-cyclohexylhexyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-2089 having formula (IIIa-3):    3-amino-3-ethyl-5-[5-(4-cyclohexylbutanoyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-2097 having formula (IIIa-3):    3-amino-3-ethyl-5-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]pentylphosphonic    acid, and-   Exemplification compound number 5-2105 having formula (IIIa-3):    3-amino-3-ethyl-5-[5-(6-cyclohexylhexanoyl)thiophen-2-yl]pentylphosphonic    acid, and-   Exemplification compound number 5-463 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[4-(4-fluorophenoxy)butyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-479 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[4-(4-methoxyphenoxy)butyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-594 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(4-benzyloxybutyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1348 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(4-fluorophenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-1349 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(4-methylphenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-1350 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(4-ethylphenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-1351 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(4-trifluoromethylphenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-1352 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(4-methoxyphenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-1353 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(4-methoxyphenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-1354 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(4-methylthiophenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-1476 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[4-(3-fluorophenoxy)butanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-1477 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[4-(4-fluorophenoxy)butanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-1478 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[4-(4-chlorophenoxy)butanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-1480 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[4-(3-methylphenoxy)butanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-1481 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[4-(4-methylphenoxy)butanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-1490 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[4-(3-trifluoromethylphenoxy)butanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-1491 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[4-(4-trifluoromethylphenoxy)butanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-1492 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[4-(3-methoxyphenoxy)butanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-1493 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[4-(4-methoxyphenoxy)butanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-1504 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[4-(3-methylthiophenoxy)butanoyl]thiophen-2-yl)pentylphosphonic    acid,-   Exemplification compound number 5-1505 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[4-(4-methylthiophenoxy)butanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-1521 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[4-(3,4-dimethylphenoxy)butanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-1522 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[4-(3,5-dimethylphenoxy)butanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-2093 having formula (IIIa-3):    3-amino-3-ethyl-5-[5-(4-phenylbutanoyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-2101 having formula (IIIa-3):    3-amino-3-ethyl-5-[5-(5-phenylpentanoyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-2109 having formula (IIIa-3):    3-amino-3-ethyl-5-[5-(6-phenylhexanoyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-2328 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(3-fluorophenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-2329 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(3,4-difluorophenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-2330 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(3,5-difluorophenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-2331 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(3-chlorophenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-2332 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(4-chlorophenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-2333 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(3,4-dichlorophenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-2334 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(3,5-dichlorophenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-2335 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(3-methylphenyl)pentanoyl]thiophen-2-yl    }pentylphosphonic acid,-   Exemplification compound number 5-2336 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(3,4-dimethylphenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-2337 having formula (IIIa-3):    3-amino-3-methyl-5-(5-[5-(3,5-dimethylphenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-2338 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(3-trifluoromethylphenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-2339 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(3,4-ditrifluoromethylphenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-2340 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(3,5-ditrifluoromethylphenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-2341 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(3-methoxyphenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-2342 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(3,4-dimethoxyphenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-2343 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(3,5-dimethoxyphenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-2344 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(3,4,5-trimethoxyphenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-2345 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(3-acetylphenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid, and-   Exemplification compound number 5-2346 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(4-acetylphenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid.

The exemplification compounds numbers of the most preferred compoundsinclude:

-   Exemplification compound number 5-84 having formula (IIIa-1):    3-amino-3-methyl-5-[5-(5-phenylpentyl)furan-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-770 having formula (IIIa-1):    3-amino-3-methyl-5-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-824 having formula (IIIa-1):    3-amino-3-methyl-5-[5-(5-phenylpent-1-ynyl)furan-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1072 having formula (IIIa-1):    3-amino-3-methyl-5-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1331 having formula (IIIa-1):    3-amino-3-methyl-5-[5-(5-cyclohexylpentanoyl)furan-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-2278 having formula (IIIa-1):    3-amino-3-methyl-5-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]furan-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-824 having formula (IIIa-2):    3-amino-3-methyl-5-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1063 having formula (IIIa-2):    3-amino-3-methyl-5-{1-methyl-5-([3-(4-methyl)phenoxyprop-1-ynyl]pyrrol-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-1072 having formula (IIIa-2):    3-amino-3-methyl-5-[1-methyl-5-(4-cyclohexyloxybut-1-ynyl)pyrrol-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-2278 having formula (IIIa-2):    3-amino-3-methyl-5-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]pyrrol-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-1344 having formula (IIIa-2):    3-amino-3-methyl-5-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   Exemplification compound number5-1331 having formula (IIIa-2):    3-amino-3-methyl-5-[1-methyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1330 having formula (IIIa-2):    3-amino-3-methyl-5-[1-methyl-5-(4-phenylbutanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1329 having formula (IIIa-2):    3-amino-3-methyl-5-[1-methyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   Exemplification compound number 8-12 having formula (IIIa-4)    3-amino-3-methyl-5-[1-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   Exemplification compound number 8-11 having formula (IIIa-4)    3-amino-3-methyl-5-[1-ethyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   Exemplification compound number 8-10 having formula (IIIa-4)    3-amino-3-methyl-5-[1-ethyl-5-(4-phenylbutanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   Exemplification compound number 8-9 having formula (IIIa-4)    3-amino-3-methyl-5-[1-ethyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-71 having formula (IIIa-3)    3-amino-3-methyl-5-[5-(4-cyclohexylbutyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-98 having formula (IIIa-3)    3-amino-3-methyl-5-[5-(5-cyclohexylpentyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-152 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(5-phenylpentyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-400 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(4-cyclohexyloxybutyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-463 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[4-(4-fluorophenoxy)butyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-479 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[4-(4-methoxyphenoxy)butyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-594 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(4-benzyloxybutyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1329 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(4-cyclohexylbutanoyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1330 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(4-phenylbutanoyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1331 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1344 having formula (IIIa-3):    3-amino-3-methyl-5-[5-(5-phenylpentanoyl)thiophen-2-yl]pentylphosphonic    acid,-   Exemplification compound number 5-1348 having formula (IIIa-3):    3-amino-3-methyl-5-{5-[5-(4-fluorophenyl)pentanoyl]thiophen-2-yl}pentylphosphonic    acid,-   Exemplification compound number 5-1764 having formula (IIIa-3):    3-amino-3-ethyl-5-[5-(5-cyclohexylpentyl)thiophen-2-yl]pentylphosphonic    acid, and-   Exemplification compound number 5-2097 having formula (IIIa-3):    3-amino-3-ethyl-5-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]pentylphosphonic    acid.

The compounds of formulae (I), (II) and (III) of the present inventioncan be prepared according to the methods described hereinafter.

(Method A)

Method A is a process for the preparation of compounds of formula (I)which include compounds of formula (Ic) wherein Y is an ethynylenegroup, compounds of formula (Id) wherein Y is a vinylene group,compounds of formula (Ie) wherein Y is an ethylene group, compounds offormula (If) wherein Y is a group of formula —CO—CH₂—, compounds offormula (Ig) wherein Y is a group of formula —CH(OH)—CH₂— and compoundsof formula (Ih) wherein Y is an aryl group or an aryl group substitutedwith from 1 to 3 substituents selected from Substituent group (a).

In the above reaction scheme R¹, R², R³, R⁴, R⁵, R⁶, R⁷, X, Z, and nhave the same meanings as those indicated hereinbefore. R⁸ represents abromine or iodine atom. R⁵ _(a) represents the same meanings as thoseindicated for R⁵ or is a group corresponding to R⁵ wherein it may haveone or more protected amino, hydroxyl, and/or carboxyl groups when theR⁵ group has one or more amino, hydroxyl and/or carboxyl groups. RingY^(a) represents an aryl group or an aryl group substituted with from 1to 3 substituents selected from Substituent group (a).

The protecting group of the amino group in the definition of R⁵ _(a) isnot particularly restricted, provided that the protecting group of theamino group can generally be used in organic chemistry, and has the samemeanings as those indicated hereinbefore. The protecting group of theamino group is preferably a lower alkoxycarbonyl group and mostpreferably a tert-butoxycarbonyl group.

The protecting group of the hydroxyl group in the definition of R⁵ _(a)is not particularly restricted, provided that the protecting group ofthe hydroxyl group can generally be used in organic chemistry and, forexample, has the same meanings as those indicated in the definition ofthe “general protecting group in chemical reactions related to the esterof a hydroxyl group”. The protecting group of the hydroxyl group ispreferably a lower aliphatic acyl group, aromatic acyl group, loweralkoxycarbonyl group or (lower alkoxy) methyl group; more preferably alower aliphatic acyl group or (lower alkoxy)methyl group and mostpreferably an acetyl or methoxymethyl group.

The protecting group of the carboxyl group in the definition of R⁵ _(a)is not particularly restricted, provided that the protecting group ofthe carboxyl group can generally be used in organic chemistry, and has,for example, the same meanings as those indicated in the definition ofthe “general protecting group in chemical reactions related to the esterof a carboxyl group”. The protecting group of the carboxyl group ispreferably a lower alkyl group and most preferably a methyl group.

Step A1

Step A1 is a process for the preparation of compounds of general formula(V). Step A1 is accomplished by the reaction of a compound of generalformula (IV) with a brominating or iodinating agent in the presence orabsence of a base in an inert solvent.

The inert solvent employed in the above reaction is not particularlyrestricted provided that it has no adverse effect on the reaction and,for example, can be a halogenated hydrocarbon such as dichloromethane,chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, ordichlorobenzene.; an ether such as diethyl ether, diisopropyl ether,tetrahydrofuran, dioxane, dimethoxyethane, or di(ethylene glycol)dimethyl ether; or an amide such as formamide, N,N-dimethylformamide,N,N-dimethylacetamide, or hexamethylphosphoric triamide. In thebromination reaction the inert solvent is preferably an amide (mostpreferably N,N-dimethylformamide). In the iodination reaction the inertsolvent is preferably a halogenated hydrocarbon (most preferablydichloromethane or chloroform).

The brominating reagent employed in the above reaction is notparticularly restricted and, for example, can be a brominating reagentdescribed in “Comprehensive Organic Transformation” (Larlock, VCH, pagefrom 316 to 317). The preferred brominating reagent isN-bromosuccinimide.

The iodinating reagent employed in the above reaction is notparticularly restricted and, for example, can be an iodinating reagentdescribed in “Comprehensive Organic Transformation” (Larlock, VCH, pagefrom 317 to 318). The preferred iodinating reagent is iodine.

The base employed in the above reaction is not particularly restrictedprovided that it has no adverse effect on substituent(s) other thanhalogen atoms, and can be, for example, an alkali metal carbonate suchas lithium carbonate, sodium carbonate, or potassium carbonate; analkali metal hydrogencarbonate such as lithium hydrogencarbonate, sodiumhydrogencarbonate, or potassium hydrogencarbonate; a metal alkoxide suchas lithium methoxide, sodium methoxide, sodium ethoxide, or potassiumtert-butoxide; an organic amine such as triethylamine, tributylamine,diisopropylethylamine, N-methylmorpholine, pyridine, 2,6-lutidine,4-(N,N-dimethylamino)pyridine, N,N-dimethylaniline, N,N-diethylaniline,1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2,2,2]octane (DABCO),or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU); or an organometallic basesuch as butyllithium, lithium diisopropylamide (LDA) or lithiumbis(trimethylsilyl)amide; or a combination of the bases indicatedhereinbefore. The base is preferably an organic amine (most preferablypyridine).

The reaction temperature depends on the starting material, thebrominating or iodinating reagent, the solvent and the like employed inthe above reaction and is generally between −78° C. and 150° C.,preferably between −20° C. and 100° C. (most preferably between 0° C.and 60° C.).

The reaction time depends on the reaction temperature, the startingmaterial, the reagent and the solvent employed in the above reaction andis generally from 5 minutes to 60 hours, preferably from 15 minutes to24 hours (most preferably from 30 minutes to 4 hours).

After the reaction, the desired compound of Step A1 and those of StepsA2˜A7 described hereinafter can be isolated from the reaction mixture byconventional treatments, for example, neutralization of the reactionmixture, if necessary, or filtration of the reaction mixture wheninsoluble material is present in the reaction mixture, addition of asolvent immiscible with water such as ethyl acetate to the neutralizedsolution or the filtrate, washing the resulting organic layer withwater, separation of the organic layer containing the desired compound,drying of the organic layer over anhydrous magnesium sulfate, anhydroussodium sulfate or the like, and then evaporation of the organic solventto give the desired product. The product thus obtained, if necessary, isfurther purified by conventional treatments, for example byrecrystallization or reprecipitation, or by conventional procedures inorganic chemistry, for example, absorption column chromatography usingcarrier such as silica gel, alumina, or Florisil consisting of magnesiumand silica gel; partition column chromatography using a syntheticabsorbent such as Sephadex LH-20 (product of Pharmacia Co., Ltd.),Amberlite XAD-11 (product of Rohm & Hass Co., Ltd.), or Diaion HP-20(product of Mitsubishi Chemicals Co., Ltd.); ion exchangechromatography; normal phase or reversed phase column chromatographyusing silica gel or alkylated silica gel (preferably high performanceliquid column chromatography); or an appropriate combination of thesechromatographic techniques; and elution using an appropriate solvent toisolate and purify the desired product.

Step A2

Step A2 is a process for the preparation of compounds of general formula(Ic). Step A2 is accomplished by the Sonogashira coupling reaction of acompound of general formula (V) with a compound of formula (VI) in thepresence of a base and a palladium catalyst in an inert solvent under anatmosphere of nitrogen, followed by removal, if necessary, of one ormore protecting groups of the hydroxyl, amino and/or carboxyl group.

The inert solvent employed in the above reaction is not particularlyrestricted provided that it has no adverse effect on the reaction and,for example, is an aliphatic hydrocarbon such as hexane, heptane,ligroin, or petroleum ether; an aromatic hydrocarbon such as benzene,toluene, or xylene; a halogenated hydrocarbon such as dichloromethane,chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, ordichlorobenzene; an ester such as ethyl formate, ethyl acetate, propylacetate, butyl acetate, or diethyl carbonate; an ether such as diethylether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, ordi(ethylene glycol) dimethyl ether; a ketone such as acetone, methylethyl ketone, methyl isobutyl ketone, isophorone, or cyclohexanone; anitrile such as acetonitrile or isobutyronitrile; an amide such asformamide, N,N-dimethylformamide, N,N-dimethylacetamide, orhexamethylphosphoric triamide; a sulfoxide such as dimethyl sulfoxide ora sulfone such as sulfolane. The inert solvent is preferably an ether,an amide or a sulfoxide (most preferably an ether or amide). In somecases the presence of a small amount of water in the solvent may enhancethe rate of the reaction.

The base employed in the above reaction is not particularly restrictedprovided that it can generally be used for the Sonogashira couplingreaction and, for example, is an alkali metal carbonate such as lithiumcarbonate, sodium carbonate, or potassium carbonate; an alkali metalhydrogencarbonate such as lithium hydrogencarbonate, sodiumhydrogencarbonate, or potassium hydrogencarbonate; an alkali metalhydride such as lithium hydride, sodium hydride, or potassium hydride;an alkali metal hydroxide such as lithium hydroxide, sodium hydroxide,or potassium hydroxide; an alkali metal alkoxide such as lithiummethoxide, sodium methoxide, sodium ethoxide, or potassiumtert-butoxide: or an organic amine such as triethylamine, tributylamine,diisopropylethylamine, N-methylmorpholine, pyridine,4-(N,N-dimethylamino)pyridine, N,N-dimethylaniline, N,N-diethylaniline,1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2,2,2]octane (DABCO),or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The base is preferably anorganic amine (most preferably triethylamine).

The palladium catalyst employed above reaction is not particularlyrestricted provided that it can generally be used in the Sonogashiracoupling reaction and, for example, can be a palladium salt such aspalladium acetate, palladium chloride, palladium carbonate; a palladiumsalt complex such as dichlorobis(triphenylphosphine)palladium complexwhich is complexed by a ligand; or palladium-charcoal. In addition,copper (I) iodide and/or benzyltriethylammonium chloride as an additivereagent can increase the yield of the desired product.

The reaction temperature depends on the starting material, base, solventand the like employed in the above reaction and is generally between−20° C. and 200° C., (preferably between 0° C. and 120° C.).

The reaction time depends on the starting material, base, solvent,reaction temperature, and the like employed in the above reaction and isgenerally from 5 minutes to 48 hours (preferably from 15 minutes to 24hours).

The removal of the protecting groups of the hydroxyl, amino and/orcarboxyl group in R¹, R², and R³, is carried out by the same procedureas that indicated hereinafter in the removal of the protecting group inStep A7.

If necessary, the desired product (Ic) of Step A2 can be isolated andpurified by conventional procedures, for example, recrystallization orreprecipitation or by conventional purification procedures in organicchemistry, for example, an appropriate combination of variouschromatographic techniques and elution using an appropriate solvent.

Step A3

Step A3 is a process for the preparation of compounds of general formula(Id). Step A3 is accomplished by a reduction reaction (preferablycatalytic reduction under an atmosphere of hydrogen) of a compound ofgeneral formula (Ic) in an inert solvent, followed by, removal, ifnecessary, of one or more protecting groups of the hydroxyl, aminoand/or carboxyl group. The removal of said protecting group is carriedout by the same procedure as that indicated hereinafter in the removalof the protecting group in Step A7.

The inert solvent employed in the above reaction is not particularlyrestricted provided that it has no adverse effect on the reaction and,for example, is an aliphatic hydrocarbon such as hexane, heptane,ligroin, or petroleum ether; an aromatic hydrocarbon such as benzene,toluene, or xylene; a halogenated hydrocarbon such as dichloromethane,chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, ordichlorobenzene; an ester such as methyl acetate, ethyl acetate, propylacetate, butyl acetate, or diethyl carbonate; an ether such as diethylether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, ordi(ethylene glycol) dimethyl ether; an alcohol such as methanol,ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol,isoamyl alcohol, di(ethylene glycol), glycerin, octanol, cyclohexanol,or methyl cellosolve; an organic acid such as acetic acid orhydrochloric acid; water; or a mixture of water and a solvent indicatedhereinbefore. The inert solvent is preferably an ether or alcohol (mostpreferably methanol).

The catalyst employed in the above catalytic reduction is notparticularly restricted provided that it can generally be used for thereduction of a triple bond to a double bond, and preferably is apalladium-type catalyst such as palladium-calcium carbonate,palladium-aluminum oxide, palladium-charcoal, or palladium-bariumsulfate, or a rhodium-type catalyst such as rhodium-aluminum oxide. Themore preferred catalyst is palladium-calcium carbonate. In addition, thecatalyst employed in the above reaction can be deactivated bythe-addition of a basic aromatic compound such as pyridine or quinoline;or an amine such as ammonia or triethylamine (preferably quinoline) inthe solvent in order to accomplish reduction of an ethynylene group to avinylene group and to avoid reduction of an ethynylene group to anethylene group.

The pressure of hydrogen is not particularly restricted. It is generallybetween from 1 to 10 atmospheric pressures, and preferably 1 atmosphericpressure.

The reaction temperature depends on the starting material, catalyst,solvent and the like employed in the above reaction and is generallybetween −20° C. and 200° C., (preferably between 0° C. and 100° C.)

The reaction time depends on the starting material, catalyst, solvent,reaction temperature, and the like employed in the above reaction and isgenerally from 5 minutes to 96 hours (preferably from 15 minutes to 72hours).

If necessary, the desired product (Id) of Step A3 can be isolated andpurified by conventional procedures, for example recrystallization orreprecipitation, or by conventional purification procedures in organicchemistry, for example, an appropriate combination of variouschromatographic techniques and elution using an appropriate solvent.

Step A4

Step A4 is a process for the preparation of compounds of general formula(Ie). Step A4 is accomplished by a reduction reaction (preferablycatalytic reduction under an atmosphere of hydrogen) of a compound ofgeneral formula (Id) in an inert solvent, followed by removal, ifnecessary, of one or more protecting groups of the hydroxyl, aminoand/or carboxyl group. The removal of said protecting group is carriedout by the same procedure as that indicated hereinafter in the removalof the protecting group in Step A7.

The inert solvent employed in the above reaction is not particularlyrestricted provided that it has no adverse effect on the reaction and,for example, can be the same solvent as that indicated in Step A3hereinbefore. The inert solvent is preferably an ester, ether or alcohol(most preferably ethyl acetate or methanol).

The catalyst employed in the above catalytic reduction is notparticularly restricted provided that it can generally be used forcatalytic reductions and, for example, can be a mixture or compound ofpalladium such as palladium-charcoal, palladium black, palladiumhydroxide, or palladium-barium sulfate; a platinum compound such asplatinum oxide or platinum black; a mixture of a rhodium compound suchas rhodium-aluminum oxide or triphenylphosphine-rhodium chloride; or atype of nickel such as Raney nickel.

The pressure of hydrogen is not particularly restricted. It is generallybetween from 1 to 10 atmospheric pressures, and preferably 1 atmosphericpressure.

The reaction temperature depends on the starting material, catalyst,solvent and the like employed in the above reaction and is generallybetween −20° C. and 200° C., (preferably between 0° C. and 100° C.).

The reaction time depends on the starting material, catalyst, solvent,reaction temperature, and the like employed in the above reaction and isgenerally from 5 minutes to 96 hours (preferably from 15 minutes to 72hours).

If necessary, the desired product (Ie) of Step A4 can be isolated andpurified by conventional procedures, for example recrystallization orreprecipitation, or by conventional purification procedures in organicchemistry, for example, an appropriate combination of variouschromatographic techniques and elution using an appropriate solvent.

Step A3a

Step A3a is a process for the preparation of compounds of generalformula (Ie) without employing the two steps of Step A3 and Step A4.Step A3a is accomplished by a reduction reaction (preferably catalyticreduction under an atmosphere of hydrogen) of a compound of generalformula (Ic) in an inert solvent, followed by removal, if necessary, ofone or more protecting groups of the hydroxyl, amino and/or carboxylgroup.

The inert solvent and catalyst employed in the above reduction reactionare not particularly restricted provided that they can be generally usedin catalytic reduction reactions, and they can be the same solvent andcatalyst as those indicated in Step A4.

The pressure of hydrogen is not particularly restricted. It is generallybetween from 1 to 10 atmospheric pressures, and preferably 1 atmosphericpressure.

The reaction temperature depends on the starting material, catalyst,solvent and the like employed in the above reaction and is generallybetween −20° C. and 200° C., (preferably between 0° C. and 100° C.)

The reaction time depends on the starting material, catalyst, solvent,reaction temperature, and the like employed in the above reaction and isgenerally from 5 minutes to 96 hours (preferably from 15 minutes to 72hours).

Step A5

Step A5 is a process for the preparation of compounds of general formula(If). Step A5 is accomplished by an addition reaction of water to acompound of general formula (Ic) in an inert solvent using an acidcatalyst, followed by removal, if necessary, of one or more protectinggroups of the hydroxyl, amino and/or carboxyl group. The removal of saidprotecting group is carried out by the same procedure as that indicatedhereinafter in the removal of the protecting group in Step A7.

The inert solvent employed in the above reaction is not particularlyrestricted provided that it has no adverse effect on the reaction and,for example, is an aliphatic hydrocarbon such as hexane, heptane,ligroin, or petroleum ether; an aromatic hydrocarbon such as benzene,toluene, or xylene; a halogenated hydrocarbon such as dichloromethane,chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, ordichlorobenzene; an ester such as ethyl formate, ethyl acetate, propylacetate, butyl acetate, or diethyl carbonate; an ether such as diethylether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, ordi(ethylene glycol) dimethyl ether; an alcohol such as methanol,ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol,isoamyl alcohol, di(ethylene glycol), glycerin, octanol, cyclohexanol,or methyl cellosolve; a ketone such as acetone, methyl ethyl ketone,methyl isobutyl ketone, isophorone, or cyclohexanone; water; or amixture of the solvents indicated hereinbefore. The inert solvent ispreferably an alcohol.

The acid catalyst employed in the above reaction is not particularlyrestricted provided that it can generally be used as an acid catalystand can be a Bronsted acid, for example, an inorganic acid such ashydrochloric acid, hydrobromic acid, sulfuric acid, perchloric acid, orphosphoric acid; or an organic acid such as acetic acid, formic acid,oxalic acid, methanesulfonic acid, p-toluenesulfonic acid,camphorsulfonic acid, trifluoroacetic acid, or trifluoromethanesulfonicacid; or, for example, a Lewis acid such as zinc chloride, tintetrachloride, boron trichloride, boron trifluoride, or borontribromide; or an acidic ion-exchange resin. The acid catalyst ispreferably an inorganic acid.

The reaction temperature depends on the starting material, catalyst,solvent and the like employed in the above reaction and is generallybetween −20° C. and 200° C., (preferably between 0° C. and 100° C.)

The reaction time depends on the starting material, catalyst, solvent,reaction temperature, and the like employed in the above reaction and isgenerally from 5 minutes to 96 hours (preferably from 15 minutes to 72hours).

Step A6

Step A6 is a process for the preparation of compounds of general formula(Ig). Step A6 is accomplished by reduction of the CO group of a compoundof general formula (If) to a—CH(OH) group in an inert solvent, followedby removal, if necessary, of one or more protecting groups of thehydroxyl, amino and/or carboxyl group. The removal of said protectinggroup is carried out by the same procedure as that indicated hereinafterin the removal of the protecting group in Step A7.

The inert solvent employed in the above reaction is not particularlyrestricted provided that it has no adverse effect on the reaction and,for example, is an aliphatic hydrocarbon such as hexane, heptane,ligroin, or petroleum ether; an aromatic hydrocarbon such as benzene,toluene, or xylene; a halogenated hydrocarbon such as chloroform,dichloromethane, 1,2-dichloroethane, or carbon tetrachloride; an ethersuch as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane,dimethoxyethane, or di(ethylene glycol) dimethyl ether; an alcohol suchas methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol,tert-butanol, isoamyl alcohol, di(ethylene glycol), glycerin, octanol,cyclohexanol, or methyl cellosolve. The inert solvent is preferably anether or alcohol (most preferably methanol or ethanol).

The reducing agent employed in the above reaction is not particularlyrestricted provided that it can reduce a CO group to a CH(OH) group and,for example, is an alkali metal borohydride such as sodium borohydride,lithium borohydride, or sodium cyanoborohydride; or an aluminum hydridecompound such as diisobutylaluminum hydride, lithium aluminum hydride,or lithium triethoxyaluminum hydride. The reducing agent is preferablyan alkali metal borohydride (most preferably sodium borohydride).

The reaction temperature depends on the starting material, reducingagent, solvent and the like employed in the above reaction and isgenerally between −10° C. and 100° C., (preferably between −20° C. and20° C.).

The reaction time depends on the starting material, reducing agent,solvent, reaction temperature, and the like employed in the abovereaction and is generally from 10 minutes to 48 hours (preferably from30 minutes to 12 hours).

Step A7

Step A7 is a process for the preparation of compounds of general formula(Ih) . Step A7 is accomplished by the Suzuki coupling reaction of acompound of general formula (V) with a compound of general formula(VIIa) or (VIIb), followed by removal, if necessary, of-one or moreprotecting groups of the hydroxyl, amino and/or carboxyl group.

The reaction temperature depends on the starting material, solvent andthe like employed in the above reaction and is generally between 0° C.and 150° C. (preferably between 10° C. and 100° C.).

The reaction time depends on the starting material, solvent, reactiontemperature, and the like employed in the above reaction and isgenerally from 15 minutes to 24 hours (preferably from 30 minutes to 12hours).

The solvent, base and palladium catalyst employed in the above reactionare the same as those indicated for the Sonogashira coupling reaction inStep A2 hereinbefore.

If necessary, the desired product (Ih) of Step A7 can be isolated andpurified by conventional procedures, for example recrystallization orreprecipitation, or by conventional purification procedures in organicchemistry, for example, an appropriate combination of variouschromatographic techniques and elution using an appropriate solvent.

The reaction conditions for removing the protecting group depend on theprotecting group of the hydroxyl, amino and/or carboxyl group. Theremoval reaction of these protecting groups can be carried out byprocedures known to those skilled in organic chemistry, for example,indicated by T. W. Green (Protective groups in Organic Synthesis, JohnWiley. & Sons) and J. F. W. McOmis (Protective groups in OrganicChemistry, Plenum Press) and, for example, can be accomplished by thefollowing procedures.

When the protecting group of the amino group is a silyl group, saidprotecting group can be usually removed by treatment with a compoundwhich can produce fluoride ions, such as tetrabutylammonium fluoride,hydrofluoric acid, hydrofluoric acid-pyridine, or potassium fluoride.

The inert solvent employed in the above reaction is not particularlyrestricted provided that it has no adverse effect on the reaction and,for example, is preferably an ether such as diethyl ether, diisopropylether, tetrahydrofuran, dioxane, dimethoxyethane, or di(ethylene glycol)dimethyl ether.

The reaction temperature and reaction time are not particularlyrestricted and are generally between 0° C. and 50° C. and from 10minutes to 18 hours.

When the protecting group of the amino group is an aliphatic acyl,aromatic acyl, or alkoxycarbonyl group or a substituted methylene groupwhich can form a Schiff base, said protecting group can be removed bytreatment with a base or acid in the presence of a solvent containingwater.

The acid employed in the above reaction is not particularly restrictedprovided that it has no adverse effect on the reaction and can generallybe used as an acid, and, for example, is an inorganic acid such ashydrobromic acid, hydrochloric acid, sulfuric acid, perchloric acid,phosphoric acid or nitric acid and preferably hydrochloric acid.

The base employed in the above reaction is not particularly restrictedprovided that it has no adverse effect on the reaction and can generallybe used as a base, and, for example, is an alkali metal carbonate suchas lithium carbonate, sodium carbonate, or potassium carbonate; analkali metal hydroxide such as lithium hydroxide, sodium hydroxide, orpotassium hydroxide; a metal alkoxide such as lithium methoxide, sodiumethoxide, or potassium tert-butoxide; or a form of ammonia such asaqueous ammonia solution, or concentrated ammonia in methanol; and ispreferably an alkali metal hydroxide.

The inert solvent employed in the above reaction is not particularlyrestricted provided that it can generally be used in hydrolysisreactions and, for example, is an alcohol such as methanol, ethanol,n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, isoamylalcohol, di(ethylene glycol), glycerin, octanol, cyclohexanol, or methylcellosolve; an ether such as diethyl ether, diisopropyl ether,tetrahydrofuran, dioxane, dimethoxyethane, or di(ethylene glycol)dimethyl ether; water; or a mixture of water and a solvent indicatedhereinbefore. The inert solvent is preferably a mixture of an ether oralcohol and water (most preferably a mixture of tetrahydrofuran,dioxane, ethanol or methanol and water).

The reaction temperature and reaction time depend on the startingmaterial, solvent, acid or base and the like employed in the abovereaction and are not particularly restricted. They are generally between0° C. and 150° C. and from 1 hour to 10 hours respectively in order toavoid side reactions.

When the protecting group of the amino group is an aralkyl oraralkyloxycarbonyl group, said protecting group can usually be removedby treatment with a reducing agent (preferably by catalytic reduction inthe presence of a catalyst at room temperature) or an oxidizing agent inan inert solvent.

The inert solvent employed in the above catalytic reduction is notparticularly restricted provided that it has no adverse effect on thereaction and, for example, is an aliphatic hydrocarbon such as hexane,heptane, ligroin, or petroleum ether; an aromatic hydrocarbon such astoluene, benzene, or xylene; an ester such as methyl acetate, ethylacetate, propyl acetate, butyl acetate, or diethyl carbonate; an ethersuch as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane,dimethoxyethane, or di(ethylene glycol) dimethyl ether; an alcohol suchas methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol,tert-butanol, isoamyl alcohol, di(ethylene glycol), glycerin, octanol,cyclohexanol, or methyl cellosolve; an organic acid such as acetic acid;water; or a mixture of water and a solvent indicated hereinbefore. Theinert solvent is preferably an alcohol, ether, organic acid or water(most preferably an alcohol or organic acid).

The catalyst employed in the above catalytic reduction is notparticularly restricted provided that it can generally be used forcatalytic reductions, and is preferably palladium-charcoal, Raneynickel, platinum oxide, platinum black, rhodium-aluminum oxide,triphenylphosphine-rhodium chloride or palladium-barium sulfate.

The pressure of hydrogen is not particularly restricted. It is generallybetween from 1 to 10 atmospheric pressures.

The reaction temperature and reaction time depend on the startingmaterial, catalyst, solvent and the like employed in the above reactionand are generally between 0° C. and 100° C. and from 5 minutes to 24hours respectively.

The inert solvent in the removal reaction using an oxidizing agent isnot particularly restricted provided that it has no adverse effect onthe reaction and, for example, is a halogenated hydrocarbon such aschloroform, dichloromethane, 1,2-dichloroethane, or carbontetrachloride; a nitrile such as acetonitrile; an ether such as diethylether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, ordi(ethylene glycol) dimethyl ether; a ketone such as acetone; an amidesuch as formamide, dimethylformamide, dimethylacetamide, orhexamethylphosphoric triamide; a sulfoxide such as dimethyl sulfoxide;or sulfolane. The inert solvent is preferably a halogenated hydrocarbon,ether or sulfoxide (most preferably a halogenated hydrocarbon orsulfoxide).

The oxidizing agent employed in the above reaction is not particularlyrestricted provided that it can usually be used as an oxidizing agentand has no adverse effect on the reaction, and is preferably potassiumpersulfate, sodium persulfate, ceric ammonium nitrate (CAN), or2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ).

The reaction temperature and reaction time depend on the startingmaterial, catalyst, solvent and the like employed in the above reactionand are generally between 0° C. and 150° C. and from 10 minutes to 24hours respectively.

In addition, when the protecting group of the amino group is an aralkylgroup, said protecting group can be also removed by treatment with anacid in an inert solvent.

The acid employed in the above reaction is not particularly restrictedprovided that it can generally be used as an acid catalyst and is, forexample, a Brφnsted acid (for example, an inorganic acid such ashydrochloric acid, hydrobromic acid, sulfuric acid, perchloric acid, orphosphoric acid; or an organic acid such as acetic acid, formic acid,oxalic acid, methanesulfonic acid, p-toluenesulfonic acid,camphorsulfonic acid, trifluoroacetic acid, or trifluoromethanesulfonicacid); or a Lewis acid such as zinc chloride, tin tetrachloride, borontrichloride, boron trifluoride, or boron tribromide; or an acidicion-exchange resin. The acid is preferably an inorganic or organic acid(most preferably hydrochloric acid, acetic acid or trifluoroaceticacid).

The inert solvent employed in the above reaction is not particularlyrestricted provided that it has no adverse effect on the reaction and,for example, is an aliphatic hydrocarbon such as hexane, heptane,ligroin, or petroleum ether; an aromatic hydrocarbon such as benzene,toluene, or xylene; a halogenated hydrocarbon such as chloroform,dichloromethane, 1,2-dichloroethane, or carbon tetrachloride; an estersuch as methyl acetate, ethyl acetate, propyl acetate, butyl acetate, ordiethyl carbonate; an ether such as diethyl ether, diisopropyl ether,tetrahydrofuran, dioxane, dimethoxyethane, or di(ethylene glycol)dimethyl ether; an alcohol such as methanol, ethanol, n-propanol,isopropanol, n-butanol, isobutanol, tert-butanol, isoamyl alcohol,di(ethylene glycol), glycerin, octanol, cyclohexanol, or methylcellosolve; an amide such as formamide, dimethylformamide,dimethylacetamide, or hexamethylphosphoric triamide; water; or a mixtureof the solvents indicated hereinbefore. The inert solvent is preferablyan ether, alcohol, or water (most preferably dioxane, tetrahydrofuran,ethanol or water).

The reaction temperature depends on the starting material, acid, solventand the like employed in the above reaction and is generally between−20° C. and the boiling point of the solvent (preferably between 0° C.and 100° C.).

The reaction time depends on the starting material, acid, solvent,reaction temperature, and the like employed in the above reaction and isgenerally from 15 minutes to 48 hours (preferably from 30 minutes to 20hours).

When the protecting group of the amino group is an alkenyloxycarbonylgroup, said protecting group can usually be removed using a base by thesame procedure as indicated hereinbefore for the aliphatic acyl,aromatic acyl, or alkoxycarbonyl group or substituted methylene groupwhich can form a Schiff base, all of which are protecting groups for theamino group.

In addition, when the protecting group of the amino group isallyloxycarbonyl group, the reaction to remove said protecting group caneasily be carried out with fewer side reactions using palladium andtriphenylphosphine or nickel tetracarbonyl.

When the protecting group of the hydroxyl group is a silyl group, saidprotecting group can be usually removed by treatment with a compoundwhich can produce fluoride ions, such as tetrabutylammonium fluoride,hydrofluoric acid, hydrofluoric acid-pyridine, or potassium fluoride; aninorganic acid such as hydrochloric acid, hydrobromic acid, sulfuricacid, perchloric acid, or phosphoric acid; or an organic acid such asacetic acid, formic acid, oxalic acid, methanesulfonic acid,p-toluenesulfonic acid, camphorsulfonic acid, trifluoroacetic acid, ortrifluoromethanesulfonic acid (preferably hydrochloric acid).

The inert solvent employed in the removal of the protecting group withfluoride ions is not particularly restricted provided that it has noadverse effect on the reaction, and is preferably an ether such asdiethyl ether, diisopropyl ether, tetrahydrofuran, dioxane,dimethoxyethane, or di(ethylene glycol) dimethyl ether; a nitrile suchas acetonitrile or isobutyronitrile; an organic acid such as aceticacid; water; or a mixture of the solvents indicated hereinbefore. Thesolvent is preferably tetrahydrofuran.

In addition, when the protecting group is removed with fluoride ions,the addition of an organic acid such as formic acid, acetic acid, orpropionic acid increases the rate of the reaction and avoidsdecomposition of the desired product and can give good yields of theproduct.

In the removal reaction of the protecting group with fluoride ions, thereaction temperature and reaction time depend on the starting material,catalyst, solvent and the like employed in the above reaction and aregenerally between 0° C. and 100° C. (preferably 10° C. and 50° C.) andfrom 1 hour to 24 hours respectively.

In the removal reaction of the protecting group with an inorganic ororganic acid, the removal reaction can be accomplished using aninorganic or organic acid using the same conditions as those indicatedfor the case where the protecting group of the amino or imino group isan aralkyl group.

When the protecting group of the hydroxyl group is an aralkyl oraralkyloxycarbonyl group, the removal of the protecting group ispreferably accomplished by treatment with a reducing agent (preferablyby catalytic reduction in the presence of a catalyst at roomtemperature) or an oxidizing agent in an inert solvent.

In the removal reaction of the protecting group by catalytic reduction,the inert solvent is not particularly restricted provided that it has noadverse effect on the reaction and, for example, is the same inertsolvent as that indicated in the case that the protecting group of theamino or imino group is an aralkyl or aralkyloxycarbonyl group and canbe removed by catalytic reduction. The solvent is preferably an alcohol(most preferably methanol).

In the removal reaction of the protecting group by catalytic reduction,the catalyst is not particularly restricted provided that it can usuallybe used for catalytic reductions, and, for example, is the same catalystas that indicated in the case that the protecting group of the amino orimino group is an aralkyl or aralkyloxycarbonyl group and can be removedby catalytic reduction. The preferred catalyst is palladium-charcoal.

The pressure is not particularly restricted. It is generally betweenfrom 1 to 10 atmospheric pressures.

The reaction temperature and reaction time depend on the startingmaterial, catalyst, solvent and the like employed in the above reactionand are generally between 0° C. and 100° C. (preferably 20° C. and 70°C.) and from 5 minutes to 48 hours (preferably from 1 hour to 24 hours)respectively.

In the removal reaction of the protecting group with an oxidizing agent,the solvent is not particularly restricted provided that it has noadverse effect on the reaction and, for example, is the same inertsolvent as that indicated in the case that the protecting group of theamino group is an aralkyl or aralkyloxycarbonyl group and can be removedby treatment with an oxidizing reagent.

In the removal reaction of the protecting group with an oxidizing agent,the oxidizing agent is not particularly restricted provided that it canusually be used for oxidation reactions and, for example, is the samereagent as that indicated in the case that the protecting group of theamino group is an aralkyl or aralkyloxycarbonyl group and can be removedby treatment with an oxidizing agent.

The reaction temperature and reaction time depend on the startingmaterial, catalyst, solvent and the like employed in the above reactionand are generally between 0° C. and 150° C. and from 10 minutes to 24hours respectively.

When the protecting group of the hydroxyl group is an aralkyl oraralkyloxycarbonyl group, the removal of the protecting group can bealso accomplished by treatment with an alkali metal such as metalliclithium or sodium in liquid ammonia or in an alcohol such as methanol,ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol,isoamyl alcohol, di(ethylene glycol), glycerin, octanol, cyclohexanol,or methyl cellosolve at between −78° C. and 0° C.

In addition, when the protecting group of the hydroxyl group is anaralkyl or aralkyloxycarbonyl group, the removal of the protecting groupcan be accomplished by treatment with aluminium chloride-sodium iodideor an alkylsilyl halide such as trimethylsilyl iodide in a solvent.

In the removal reaction of the protecting group with aluminumchloride-sodium iodide or an alkylsilyl halide, the solvent employed inthe reaction is not particularly restricted provided that it has noadverse effect on the reaction, and preferably includes an halogenatedhydrocarbon such as dichloromethane, chloroform, or carbontetrachloride; a nitrile such as acetonitrile or a mixture of thesolvents indicated hereinbefore.

The reaction temperature and reaction time of the removal reaction usingaluminum chloride-sodium iodide or an alkylsilyl halide depend on thestarting material, solvent and the like employed in the reaction and aregenerally between 0° C. and 50° C. and from 5 minutes to 72 hoursrespectively.

In addition, when a substrate contains one or more sulfur atoms,aluminum chloride-sodium iodide is preferably used.

When the protecting group of the hydroxyl group is an aliphatic acyl,aromatic acyl or alkyoxycarbonyl group, the removal of the protectinggroup can be accomplished by treatment with a base in a solvent.

The base employed in the above reaction is not particularly restrictedprovided that it can be usually used as a base and has no adverse effecton the reaction, and is, for example, an alkali metal carbonate such aslithium carbonate, sodium carbonate, or potassium carbonate; an alkalimetal hydrogencarbonate such as lithium hydrogencarbonate, sodiumhydrogencarbonate, or potassium hydrogencarbonate; an alkali metalhydroxide such as lithium hydroxide, sodium hydroxide or potassiumhydroxide; a metal alkoxide such as lithium methoxide, sodium methoxide,sodium ethoxide, or potassium tert-butoxide; or an ammonia solution suchas aqueous ammonia or concentrated ammonia in methanol. The base ispreferably an alkali metal hydroxide, a metal alkoxide or an ammoniasolution (most preferably an alkali metal hydroxide or a metalalkoxide).

The solvent employed in the above reaction is not particularlyrestricted provided that it can be usually used for hydrolysis reactionsand, for example, is preferably an ether such as diethyl ether,diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, ordi(ethylene glycol) dimethyl ether; an alcohol such as methanol,ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol,isoamyl alcohol, di(ethylene glycol), glycerin, octanol, cyclohexanol,or methyl cellosolve; water; or a mixture of the solvents indicatedhereinbefore.

The reaction temperature and reaction time depend on the startingmaterial, base, solvent and the like employed in the reaction and aregenerally between −20° C. and 150° C. and from 1 hour to 10 hoursrespectively in order to avoid side reactions.

When the protecting group of the hydroxyl group is an alkoxymethyl,tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrofuranyl,tetrahydrothiofuranyl, or substituted ethyl group, the removal of theprotecting group is accomplished by treatment with an acid in an inertsolvent.

The acid employed in the above reaction is not particularly restrictedprovided that it can be usually used as a Brφnsted or Lewis acid and ispreferably a Brφnsted acid, for example, an inorganic acid such ashydrogen chloride, hydrochloric acid, sulfuric acid, nitric acid; or anorganic acid such as acetic acid, trifluoroacetic acid, methanesulfonicacid, or p-toluenesulfonic acid; or a Lewis acid such as borontrifluoride. The acid is more preferably hydrochloric acid or aceticacid. In the above reaction a strong-acidic cation ion-exchange resinsuch as Dowex 50W can be also used.

The inert solvent employed in the above reaction is not particularlyrestricted provided that it has no adverse effect on the reaction and,for example, is an aliphatic hydrocarbon such as hexane, heptane,ligroin, or petroleum ether; an aromatic hydrocarbon such as benzene,toluene, or xylene; a halogenated hydrocarbon such as dichloromethane,chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, ordichlorobenzene; an ester such as ethyl formate, ethyl acetate, propylacetate, butyl acetate, or diethyl carbonate; an ether such as diethylether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, ordi(ethylene glycol) dimethyl ether; an alcohol such as methanol,ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol,isoamyl alcohol, di(ethylene glycol), glycerin, octanol, cyclohexanol,or methyl cellosolve; a ketone such as acetone, methyl ethyl ketone,methyl isobutyl ketone, isophorone, or cyclohexanone; water; or amixture of the solvents indicated hereinbefore. The solvent ispreferably an ether (most preferably tetrahydrofuran) or an alcohol(most preferably methanol).

The reaction temperature and reaction time depend on the startingmaterial, acid, solvent and the like employed in the reaction and aregenerally between −10° C. and 200° C. (preferably between 0° C. and 150°C.) and from 5 minutes to 48 hours (preferably from 30 minutes to 10hours) respectively.

When the protecting group of the hydroxyl group is an alkenyloxycarbonylgroup, the removal of the protecting group can usually be accomplishedby treatment with a base according to the same conditions as thoseindicated hereinbefore in the case that the protecting group of thehydroxyl group is an aliphatic acyl, aromatic acyl or alkoxycarbonylgroup.

In addition, when protecting group of the hydroxyl group is anallyloxycarbonyl group, the protecting group can easily be removed withfewer side reactions by using palladium and triphenylphosphine orbis(methyldiphenylphosphine)(1,5-cyclooctadiene)iridium (I)hexafluorophosphate.

When the protecting group of the carboxyl group is a lower alkyl group,or a lower alkyl group substituted with from 1 to 3 aryl groups whereinthe aryl group may optionally be substituted with one or more loweralkyl, lower alkoxy, nitro group(s), halogen atom(s), or cyano group(s),the removal of the protecting group can usually be accomplished bytreatment with a base according to the same conditions as thoseindicated hereinbefore in the case that the protecting group of thehydroxyl group is an aliphatic acyl, aromatic acyl or alkoxycarbonylgroup.

When there are protecting groups of the amino, hydroxyl and/or carboxylgroups in the compounds indicated in the method A, the order of theremoval reactions of the protecting groups of the amino, hydroxyl and/orcarboxyl groups can be arbitrarily selected and the removal reactionscan be carried out in order of precedence.

In addition, if it is necessary to separate isomers, which are obtainedin each step of method A, each isomer can be isolated according to theisolation or purification procedures indicated hereinbefore after thereaction of each step in method A, or after removal of the protectinggroup in each step in method A.

The starting materials of formula (VI) and (VII) are known or can beprepared according to similar procedures to those known to those skilledin the art.

(Method B)

Method B is a process for the preparation of compounds of formula (IV),which are intermediates for the preparation of compounds of formula (I)of the present invention.

In the above reaction scheme R¹, R², R³, R⁴, R⁶, R⁷, and X have the samemeanings as those indicated hereinbefore. The group of formula —NR¹_(b)R² _(b) represents an amino group protected with a protecting grouphaving a carbonyl group. R⁹ represents a C₁–C₂₀ alkyl group, a C₂–C₂₀alkyl group interrupted with one or more heteroatoms, a C₁–C₂₀ alkylgroup substituted with one or more aryl groups or aromatic heterocyclicgroups, a C₂–C₂₀ alkynyl group, a C₃–C₂₀ alkynyl group interrupted withone or more heteroatoms, a C₂–C₂₀ alkynyl group substituted with one ormore aryl groups or aromatic heterocyclic groups, a C₂–C₂₀ alkenylgroup, a C₃–C₂₀ alkenyl group interrupted with one or more heteroatoms,a C₂–C₂₀ alkenyl group substituted with one or more aryl groups oraromatic heterocyclic groups, a C₂–C₂₀ alkyl group interrupted with oneor more heteroatoms substituted with one or more aryl groups or aromaticheterocyclic groups, or a C₃–C₁₀ cycloalkyl group m represents aninteger of from 0 to 4. Ph represents a phenyl group. Q represents ahalogen atom (preferably a chlorine, bromine or iodine atom).

The “C₁–C₂₀ alkyl group” in the above definition of R⁹ is, for example,a straight or branched chain alkyl group having from one to twentycarbon atoms such as a “lower alkyl group” indicated hereinbefore,heptyl, 1-methylhexyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl,5-methylhexyl, 1-propylbutyl, 4,4-dimethylpentyl, octyl, 1-methylheptyl,2-methylheptyl, 3-methylheptyl, 4-methylheptyl, 5-methylheptyl,6-methylheptyl, 1-propylpentyl, 2-ethylhexyl, 5,5-dimethylhexyl, nonyl,3-methyloctyl, 4-methyloctyl, 5-methyloctyl, 6-methyloctyl,1-propylhexyl, 2-ethylheptyl, 6,6-dimethylheptyl, decyl, 1-methylnonyl,3-methylnonyl, 8-methylnonyl, 3-ethyloctyl, 3,7-dimethyloctyl,7,7-dimethyloctyl, undecyl, 4,8-dimethylnonyl, dodecyl, tridecyl,tetradecyl, pentadecyl, 3,7,11-trimethyldodecyl, hexadecyl,4,8,12-trimethyltridecyl, 1-methylpentadecyl, 14-methylpentadecyl,13,13-dimethyltetradecyl, heptadecyl, 15-methylhexadecyl, octadecyl,1-methylheptadecyl, nonadecyl, icosyl, or3,7,11,15-tetramethylhexadecyl; and is preferably a C₁–C₁₀ alkyl group.

The “C₂–C₂₀ alkyl group interrupted with one or more heteroatoms” in theabove definition of R⁹ represents a C₂–C₂₀ alkyl group interrupted withone or more heteroatoms, wherein the “C₂–C₂₀ alkyl group” is included inthe “C₁–C₂₀ alkyl group” indicated hereinbefore and the alkyl group isinterrupted with the same or different one or two sulfur, oxygen ornitrogen atoms, and is, for example, a C₂–C₂₀ alkyl group interruptedwith one or two sulfur atoms such as methylthiomethyl,1-methylthioethyl, 2-methylthioethyl, ethylthiomethyl,1-methylthiopropyl, 2-methylthiopropyl, 3-methylthiopropyl,2-ethylthioethyl, 2-methyl-2-methylthioethyl, 1-methylthiobutyl,2-methylthiobutyl, 3-methylthiobutyl, 2-ethylthiopropyl,3-methyl-3-methylthiopropyl, 4-methylthiopentyl, 3-methylthiopentyl,2-methylthiopentyl,1-methylthiopentyl, 3,3-dimethylthiobutyl,2,2-dimethylthiobutyl, 1,1-dimethylthiobutyl,1-methyl-2-methylthiobutyl, 1,3-dimethylthiobutyl,2,3,-dimethylthiobutyl, -2-ethylthiobutyl, 1-methylthiohexyl,2-methylthiohexyl, 3-methylthiohexyl, 4-methylthiohexyl,5-methylthiohexyl, 1-propylthiobutyl, 4-methyl-4-methylthiopentyl,1-methylthioheptyl, 2-methylthioheptyl, 3-methylthioheptyl,4-methylthioheptyl, 5-methylthioheptyl, 6-methylthioheptyl,1-propylthiopentyl, 2-ethylthiohexyl, 5-methyl-5-methylthiohexyl,3-methylthiooctyl, 4-methylthiooctyl, 5-methylthiooctyl,6-methylthiooctyl, 1-propylthiohexyl, 2-ethylthioheptyl,6-methyl-6-methylthioheptyl, 1-methylthiononyl, 3-methylthiononyl,8-methylthiononyl, 3-ethylthiooctyl, 3-methyl-7-methylthiooctyl,7,7-dimethylthiooctyl, 4-methyl-8-methylthiononyl,3,7-dimethyl-11-methylthiododecyl, 4,8-dimethyl-12-methylthiotridecyl,1-methylthiopentadecyl, 14-methylthiopentadecyl,13-methyl-13-methylthiotetradecyl, 15-methylthiohexadecyl,1-methylthioheptadecyl or 3,7,11-trimethyl-15-methylthiohexadecyl;

a C₂–C₂₀ alkyl group interrupted with one or two oxygen atoms such asmethyloxymethyl, 1-methyloxyethyl, 2-methyloxyethyl, ethyloxymethyl,1-methyloxypropyl, 2-methyloxypropyl, 3-methyloxypropyl,2-ethyloxyethyl, 2-methyl-2-methyloxyethyl, 1-methyloxybutyl,2-methyloxybutyl, 3-methyloxybutyl, 2-ethyloxypropyl,3-methyl-3-methyloxypropyl, 4-methyloxypentyl, 3-methyloxypentyl,2-methyloxypentyl, 1-methyloxypentyl, 3,3-dimethyloxybutyl,2,2-dimethyloxybutyl, 1,1-dimethyloxybutyl, 1-methyl-2-methyloxybutyl,1,3-dimethyloxybutyl, 2,3,-dimethyloxybutyl, 2-ethyloxybutyl,1-methyloxyhexyl, 2-methyloxyhexyl, 3-methyloxyhexyl, 4-methyloxyhexyl,5-methyloxyhexyl, 1-propyloxybutyl, 4-methyl-4-methyloxypentyl,1-methyloxyheptyl, 2-methyloxyheptyl, 3-methyloxyheptyl,4-methyloxyheptyl, 5-methyloxyheptyl, 6-methyloxyheptyl,1-propyloxypentyl, 2-ethyloxyhexyl, 5-methyl-5-methyloxyhexyl,3-methyloxyoctyl, 4-methyloxyoctyl, 5-methyloxyoctyl, 6-methyloxyoctyl,1-propyloxyhexyl, 2-ethyloxyheptyl, 6-methyl-6-methyloxyheptyl,1-methyloxynonyl, 3-methyloxynonyl, 8-methyloxynonyl, 3-ethyloxyoctyl,-3-methyl-7-methyloxyoctyl, 7,7-dimethyloxyoctyl,4-methyl-8-methyloxynonyl, 3,7-dimethyl-11-methyloxydodecyl,4,8-dimethyl-12-methyloxytridecyl, 1-methyloxypentadecyl,14-methyloxypentadecyl, 13-methyl-13-methyloxytetradecyl,15-methyloxyhexadecyl, 1-methyloxyheptadecyl or3,7,11-trimethyl-15-methyloxyhexadecyl;

a C₂–C₂₀ alkyl group interrupted with one or two nitrogen atoms such asN-methylaminomethyl, 1-(N-methylamino)ethyl, 2-(N-methylamino)ethyl,N-ethylaminomethyl, 1-(N-methylamino)propyl, 2-(N-methylamino)propyl,3-(N-methylamino)propyl, 2-(N-ethylamino)ethyl,2-(N,N-dimethylamino)ethyl, 1-(N-methylamino)butyl,2-(N-methylamino)butyl, 3-(N-methylamino)butyl, 2-(N-ethylamino)propyl,3-(N,N-dimethylamino)propyl, 4-(N-methylamino)pentyl,3-(N-methylamino)pentyl, 2-(N-methylamino)pentyl,1-(N-methylamino)pentyl, 3-(N,N-dimethylamino)butyl,2-(N,N-dimethylamino)butyl, 1-(N,N-dimethylamino)butyl,1-methyl-2-(N-methylamino)butyl, 1,3-di(N-methylamino)butyl,2,3,-di(N-methylamino)butyl, 2-(N-ethylamino)butyl,1-(N-methylamino)hexyl, 2-(N-methylamino)hexyl, 3-(N-methylamino)hexyl,4-(N-methylamino)hexyl, 5-(N-methylamino)hexyl, 1-(N-propylamino)butyl,4-methyl-4-(N-methylamino)pentyl, 1-(N-methylamino)heptyl,2-(N-methylamino)heptyl, 3-(N-methylamino)heptyl,4-(N-methylamino)heptyl, 5-(N-methylamino)heptyl,6-(N-methylamino)heptyl, 1-(N-propylamino)pentyl, 2-(N-ethylamino)hexyl,5-methyl-5-(N-methylamino)hexyl, 3-(N-methylamino)octyl,4-(N-methylamino)octyl, 5-(N-methylamino)octyl, 6-(N-methylamino)octyl,1-(N-propylamino)hexyl, 2-(N-ethylamino)heptyl,6-methyl-6-(N-methylamino)heptyl, 1-(N-methylamino)nonyl,3-(N-methylamino)nonyl, 8-(N-methylamino)nonyl, 3-(N-ethylamino)octyl,3-methyl-7-(N-methylamino)octyl, 7,7-di(N-methylamino)octyl,4-methyl-8-(N-methylamino)nonyl, 3,7-dimethyl-11-(N-methylamino)dodecyl,4,8-dimethyl-12-(N-methylamino)tridecyl, 1-(N-methylamino)pentadecyl,14-(N-methylamino)pentadecyl, 13-methyl-13-(N-methylamino)tetradecyl,15-(N-methylamino)hexadecyl, 1-(N-methylamino)heptadecyl or3,7,11-trimethyl-15-(N-methylamino)hexadecyl.

The alkyl group interrupted with one or more heteroatoms is preferably aC₂–C₁₀ alkyl group interrupted with one or more heteroatoms.

The “C₁–C₂₀ alkyl group substituted with one or more aryl groups oraromatic heterocyclic groups” in the above definition of R⁹ representsthe above-indicated “C₁–C₂₀ alkyl group” substituted with from 1 to 3aryl or aromatic heterocyclic groups which are the same or different andhave the same meanings as those indicated hereinbefore.

The “C₂–C₂₀ alkynyl group” in the above definition of R⁹ is, forexample, a straight or branched chain alkynyl group having from two totwenty carbon atoms such as ethynyl, 2-propynyl, 1-methyl-2-propynyl,2-butynyl, 1-methyl-2-butynyl, 1-ethyl-2-butynyl, 3-butynyl,1-methyl-3-butynyl, 2-methyl-3-butynyl, 1-ethyl-3-butynyl, 2-pentynyl,1-methyl-2-pentynyl, 3-pentynyl, 1-methyl-3-pentynyl,2-methyl-3-pentynyl, 4-pentynyl, 1-methyl-4-pentynyl,2-methyl-4-pentynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl,heptynyl, 3-methylhexynyl, 4-methylhexynyl, 5-methylhexynyl,4,4-dimethylpentynyl, octynyl, 3-methylheptynyl, 4-methylheptynyl,5-methylheptynyl, 6-methylheptynyl, 5,5-dimethylhexynyl, nonynyl,3-methyloctynyl, 4-methyloctynyl, 5-methyloctynyl, 6-methyloctynyl,6,6-dimethylheptynyl, decynyl, 3-methylnonynyl, 8-methylnonynyl,3-ethyloctynyl, 3,7-dimethyloctynyl, 7,7-dimethyloctynyl, undecynyl,4,8-dimethylnonynyl, dodecynyl, tridecynyl, tetradecynyl, pentadecynyl,3,7,11-trimethyldodecynyl, hexadecynyl, 4,8,12-trimethyltridecynyl,14-methylpentadecynyl, 13,13-dimethyltetradecynyl, heptadecynyl,15-methylhexadecynyl, octadecynyl, nonadecynyl, icosynyl, or3,7,11,15-tetramethylhexadecynyl, and is preferably a C₁–C₁₀ alkynylgroup.

The “C₃–C₂₀ alkynyl group interrupted with one or more heteroatoms” inthe above definition of R⁹ represents a C₃–C₂₀ alkynyl group interruptedwith one or more heteroatoms, wherein the “C₃–C₂₀ alkynyl group” isincluded in the “C₁–C₂₀ alkynyl group” indicated hereinbefore and thealkynyl group is interrupted with the same or different one or twosulfur, oxygen or nitrogen atoms, and is, for example, a C₃–C₂₀ alkynylgroup interrupted with one or two sulfur atoms such as2-methylthioethynyl, 3-methylthiopropynyl, 2-ethylthioethynyl,3-methylthiobutynyl, 3-methyl-3-methylthiopropynyl,4-methylthiopentynyl, 3-methylthiopentynyl, 3,3-dimethylthiobutynyl,3-methylthiohexynyl, 4-methylthiohexynyl, 5-methylthiohexynyl,4-methyl-4-methylthiopentynyl, 3-methylthioheptynyl,4-methylthioheptynyl, 5-methylthioheptynyl, 6-methylthioheptynyl,5-methyl-5-methylthiohexynyl, 3-methylthiooctynyl, 4-methylthiooctynyl,5-methylthiooctynyl, 6-methylthiooctynyl, 6-methyl-6-methylthioheptynyl, 3-methylthiononynyl, 8-methylthiononynyl,3-ethylthiooctynyl, 3-methyl-7-methylthiooctynyl,7,7-dimethylthiooctynyl, 4-methyl-8-methylthiononynyl,3,7-dimethyl-11-methylthiododecynyl,4,8-dimethyl-12-methylthiotridecynyl, 14-methylthiopentadecynyl,13-methyl-13-methylthiotetradecynyl, 15-methylthiohexadecynyl, or3,7,11-trimethyl-15-methylthiohexadecynyl;

a C₃–C₂₀ alkynyl group interrupted with one or two oxygen atoms such as2-methyloxyethynyl, 3-methyloxypropynyl, 2-ethyloxyethynyl,3-methyloxybutynyl, 3-methyl-3-methyloxypropynyl, 4-methyloxyopentynyl,3-methyloxypentynyl, 3,3-dimethyloxybutynyl, 3-methyloxyhexynyl,4-methyloxyhexynyl, 5-methyloxyhexynyl, 4-methyl-4-methyloxypentynyl,3-methyloxyheptynyl, 4-methyloxyheptynyl, 5-methyloxyheptynyl,6-methyloxyheptynyl, 5-methyl-5-methyloxyhexynyl, 3-methyloxyoctynyl,4-methyloxyoctynyl, 5-methyloxyoctynyl, 6-methyloxyoctynyl,6-methyl-6-methyloxyheptynyl, 3-methyloxynonynyl, 8-methyloxynonynyl,3-ethyloxyoctynyl, 3-methyl-7-methyloxyoctynyl, 7,7-dimethyloxyoctynyl,4-methyl-8-methyloxynonynyl, 3,7-dimethyl-11-methyloxydodecynyl,4,8-dimethyl-12-methyloxytridecynyl, 14-methyloxypentadecynyl,13-methyl-13-methyloxytetradecynyl, 15-methyloxyhexadecynyl, or3,7,11-trimethyl-15-methyloxyhexadecynyl; or

a C₃–C₂₀ alkynyl group interrupted with one or two nitrogen atoms suchas 2-(N-methylamino)ethynyl, 3-(N-methylamino)propynyl,2-(N-ethylamino)ethynyl, 2-(N,N-dimethylamino)ethynyl,3-(N-methylamino)butynyl, 3-(N,N-dimethylamino)propynyl,4-(N-methylamino)pentynyl, 3-(N-methylamino)pentynyl,3-(N,N-dimethylamino)butynyl, 3-(N-methylamino)hexynyl,4-(N-methylamino)hexynyl, 5-(N-methylamino)hexynyl,4-methyl-4-(N-methylamino)pentynyl, 3-(N-methylamino)heptynyl,4-(N-methylamino)heptynyl, 5-(N-methylamino)heptynyl,6-(N-methylamino)heptynyl, 5-methyl-5-(N-methylamino)hexynyl,3-(N-methylamino)octynyl, 4-(N-methylamino)octynyl,5-(N-methylamino)octynyl, 6-(N-methylamino)octynyl,6-methyl-6-(N-methylamino)heptynyl, 3-(N-methylamino)nonynyl,8-(N-methylamino)nonynyl, 3-(N-ethylamino)octynyl,3-methyl-7-(N-methylamino)octynyl, 7,7-di(N-methylamino)octynyl,4-methyl-8-(N-methylamino)nonynyl,3,7-dimethyl-11-(N-methylamino)dodecynyl,4,8-dimethyl-12-(N-methylamino)tridecynyl,14-(N-methylamino)pentadecynyl,13-methyl-13-(N-methylamino)tetradecynyl, 15-(N-methylamino)hexadecynyl,or 3,7,11-trimethyl-15-(N-methylamino)hexadecynyl; preferably a C₃–C₁₀alkynyl group interrupted with one or more heteroatoms.

The “C₂–C₂₀ alkynyl group substituted with one or more aryl groups oraromatic heterocyclic groups” in the above definition of R⁹ represents aC₂–C₂₀ alkynyl group indicated hereinbefore wherein the alkynyl group issubstituted with from 1 to 3 “aryl” or “aromatic heterocyclic” groupswhich are the same or different and indicated hereinbefore.

The “C₂–C₂₀ alkenyl group” in the definition of R⁹ includes, forexample, a straight or branched chain alkenyl group having from two totwenty carbon atoms such as ethenyl, 2-propenyl, 1-methyl-2-propenyl,2-methyl-2-propenyl, 2-ethyl-2-propenyl, 2-butenyl, 1-methyl-2-butenyl,2-methyl-2-butenyl, 1-ethyl-2-butenyl, 3-butenyl, 1-methyl-3-butenyl,2-methyl-3-butenyl, 1-ethyl-3-butenyl, 2-pentenyl, 1-methyl-2-pentenyl,2-methyl-2-pentenyl, 3-pentenyl, 1-methyl-3-pentenyl,2-methyl-3-pentenyl, 4-pentenyl, 1-methyl-4-pentenyl,2-methyl-4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl,heptenyl, 1-methylhexenyl, 2-methylhexenyl, 3-methylhexenyl,4-methylhexenyl, 5-methylhexenyl, 1-propylbutenyl, 4,4-dimethylpentenyl,octenyl, 1-methylheptenyl, 2-methylheptenyl, 3-methylheptenyl,4-methylheptenyl, 5-methylheptenyl, 6-methylheptenyl, 1-propylpentenyl,2-ethylhexenyl, 5,5-dimethylhexenyl, nonenyl, 3-methyloctenyl,4-methyloctenyl, 5-methyloctenyl, 6-methyloctenyl, 1-propylhexenyl,2-ethylheptenyl, 6,6-dimethylheptenyl, decenyl, 1-methylnonenyl,3-methylnonenyl, 8-methylnonenyl, 3-ethyloctenyl, 3,7-dimethyloctenyl,7,7-dimethyloctenyl, undecenyl, 4,8-dimethylnonenyl, dodecenyl,tridecenyl, tetradecenyl, pentadecenyl, 3,7,11-trimethyldodecenyl,hexadecenyl, 4,8,12-trimethyltridecenyl, 1-methylpentadecenyl,14-methylpentadecenyl, 13,13-dimethyltetradecenyl, heptadecenyl,15-methylhexadecenyl, octadecenyl, 1-methylheptadecenyl, nonadecenyl,icosenyl, or 3,7,11,15-tetramethylhexadecenyl group; and is preferably aC₂–C₁₀ alkenyl group.

The “C₃–C₂₀ alkenyl group interrupted with one or more heteroatoms” inthe above definition of R⁹ is a “C₃–C₂₀ alkenyl group”, wherein thealkenyl group is interrupted with the same or different one or twosulfur, oxygen or nitrogen atoms and is included in the “C₂–C₂₀ alkenylgroup” indicated hereinbefore, and includes, for example, an alkenylgroup having from three to twenty carbon atoms interrupted with one ortwo sulfur atoms such as 1-methylthioethenyl, 2-methylthioethenyl,1-methylthiopropenyl, 2-methylthiopropenyl, 3-methylthiopropenyl,2-ethylthioethenyl, 2-methyl-2-methylthioethenyl, 1-methylthiobutenyl,2-methylthiobutenyl, 3-methylthiobutenyl, 2-ethylthiopropenyl,3-methyl-3-methylthiopropenyl, 4-methylthiopentenyl,3-methylthiopentenyl, 2-methylthiopentenyl, 1-methylthiopentenyl,3,3-dimethylthiobutenyl, 1-methyl-2-methylthiobutenyl,1,3-dimethylthiobutenyl, 2,3-dimethylthiobutenyl, 2-ethylthiobutenyl,1-methylthiohexenyl, 2-methylthiohexenyl, 3-methylthiohexenyl,4-methylthiohexenyl, 5-methylthiohexenyl, 1-propylthiobutenyl,4-methyl-4-methylthiopentenyl, 1-methylthioheptenyl,2-methylthioheptenyl, 3-methylthioheptenyl, 4-methylthioheptenyl,5-methylthioheptenyl, 6-methylthioheptenyl, 1-propylthiopentenyl,2-ethylthiohexenyl, 5-methyl-5-methylthiohexenyl, 3-methylthiooctenyl,4-methylthiooctenyl, 5-methylthiooctenyl, 6-methylthiooctenyl,1-propylthiohexenyl, 2-ethylthioheptenyl, 6-methyl-6-methylthioheptenyl,1-methylthiononenyl, 3-methylthiononenyl, 8-methylthiononenyl,3-ethylthiooctenyl, 3-methyl-7-methylthiooctenyl,7,7-dimethylthiooctenyl, 4-methyl-8-methylthiononenyl,3,7-dimethyl-11-methylthiododecenyl,4,8-dimethyl-12-methylthiotridecenyl, 1-methylthiopentadecenyl,14-methylthiopentadecenyl, 13-methyl-13-methylthiotetradecenyl,15-methylthiohexadecenyl, 1-methylthioheptadecenyl, or3,7,11-trimethyl-15-methylthiohexadecenyl group;

an alkenyl group having from three to twenty carbon atoms interruptedwith one or two oxygen atoms such as 1-methyloxyethenyl,2-methyloxyethenyl, 1-methyloxypropenyl, 2-methyloxypropenyl,3-methyloxypropenyl, 2-ethyloxyethenyl, 2-methyl-2-methyloxyethenyl,1-methyloxybutenyl, 2-methyloxybutenyl, 3-methyloxybutenyl,2-ethyloxypropenyl, 3-methyl-3-methyloxypropenyl, 4-methyloxypentenyl,3-methyloxypentenyl, 2-methyloxypentenyl, 1-methyloxypentenyl,3,3-dimethyloxybutenyl, 1-methyl-2-methyloxybutenyl,1,3-dimethyloxybutenyl, 2,3-dimethyloxybutenyl, 2-ethyloxybutenyl,1-methyloxyhexenyl, 2-methyloxyhexenyl, 3-methyloxyhexenyl,4-methyloxyhexenyl, 5-methyloxyhexenyl, 1-propyloxybutenyl,4-methyl-4-methyloxypentenyl, 1-methyloxyheptenyl, 2-methyloxyheptenyl,3-methyloxyheptenyl, 4-methyloxyheptenyl, 5-methyloxyheptenyl,6-methyloxyheptenyl, 1-propyloxypentenyl, 2-ethyloxyhexenyl,5-methyl-5-methyloxyhexenyl, 3-methyloxyoctenyl, 4-methyloxyoctenyl,5-methyloxyoctenyl, 6-methyloxyoctenyl, 1-propyloxyhexenyl,2-ethyloxyheptenyl, 6-methyl-6-methyloxyheptenyl, 1-methyloxynonenyl,3-methyloxynonenyl, 8-methyloxynonenyl, 3-ethyloxyoctenyl,3-methyl-7-methyloxyoctenyl, 7,7-dimethyloxyoctenyl,4-methyl-8-methyloxynonenyl, 3,7-dimethyl-11-methyloxydodecenyl,4,8-dimethyl-12-methyloxytridecenyl, 1-methyloxypentadecenyl,14-methyloxypentadecenyl, 13-methyl-13-methyloxytetradecenyl,15-methyloxyhexadecenyl, 1-methyloxyheptadecenyl, or3,7,11-trimethyl-15-methyloxyhexadecenyl group; or

an alkenyl group having from three to twenty carbon atoms interruptedwith one or two nitrogen atoms such as 1-(N-methylamino)ethenyl,2-(N-methylamino)ethenyl, 1-(N-methylamino)propenyl,2-(N-methylamino)propenyl, 3-(N-methylamino)propenyl,2-(N-ethylamino)ethenyl, 2-(N,N-dimethylamino)ethenyl,1-(N-methylamino)butenyl, 2-(N-methylamino)butenyl,3-(N-methylamino)butenyl, 2-(N-ethylamino)propenyl,3-(N,N-dimethylamino)propenyl, 4-(N-methylamino)pentenyl,3-(N-methylamino)pentenyl, 2-(N-methylamino)pentenyl,1-(N-methylamino)pentenyl, 3-(N,N-dimethylamino)butenyl,2-(N,N-dimethylamino)butenyl, 1-(N,N-dimethylamino)butenyl,1-methyl-2-(N-methylamino)butenyl, 1,3-di(N-methylamino)butenyl,2,3-di(N-methylamino)butenyl, 2-(N-ethylamino)butenyl,1-(N-methylamino)hexenyl, 2-(N-methylamino)hexenyl,3-(N-methylamino)hexenyl, 4-(N-methylamino)hexenyl,5-(N-methylamino)hexenyl, 1-(N-propylamino)butenyl,4-methyl-4-(N-methylamino)pentenyl, 1-(N-methylamino)heptenyl,2-(N-methylamino)heptenyl, 3-(N-methylamino)heptenyl,4-(N-methylamino)heptenyl, 5-(N-methylamino)heptenyl,6-(N-methylamino)heptenyl, 1-(N-propylamino)pentenyl,2-(N-ethylamino)hexenyl, 5-methyl-5-(N-methylamino)hexenyl,3-(N-methylamino)octenyl, 4-(N-methylamino)octenyl,5-(N-methylamino)octenyl, 6-(N-methylamino)octenyl,1-(N-propylamino)hexenyl, 2-(N-ethylamino)heptenyl,6-methyl-6-(N-methylamino)heptenyl, 1-(N-methylamino)nonenyl,3-(N-methylamino)nonenyl, 8-(N-methylamino)nonenyl,3-(N-ethylamino)octenyl, 3-methyl-7-(N-methylamino)octenyl,7,7-di(N-methylamino)octenyl, 4-methyl-8-(N-methylamino)nonenyl,3,7-dimethyl-11-(N-methylamino)dodecenyl,4,8-dimethyl-12-(N-methylamino)tridecenyl,1-(N-methylamino)pentadecenyl, 14-(N-methylamino)pentadecenyl,13-methyl-13-(N-methylamino)tetradecenyl, 15-(N-methylamino)hexadecenyl,1-(N-methylamino)heptadecenyl, or3,7,11-trimethyl-15-(N-methylamino)hexadecenyl group; preferably aC₃–C₁₀ alkenyl group interrupted with one or more heteroastoms.

The “C₂–C₂₀ alkenyl group substituted with one or more aryl groups oraromatic heterocyclic groups” in the above definition of R⁹ represents a“C₂–C₂₀ alkenyl group” which is indicated hereinbefore substituted withthe same or different from 1 to 3 “aryl” or “aromatic heterocyclic”groups indicated hereinbefore.

The “C₂–C₂₀ alkyl group which is interrupted with one or moreheteroatoms and substituted with one or more aryl groups or aromaticheterocyclic groups” in the above definition of R⁹ represents a “C₂–C₂₀alkyl group interrupted with one or more heteroatoms” which is indicatedhereinbefore substituted with the same or different from 1 to 3 “aryl”or “aromatic heterocyclic” groups indicated hereinbefore.

The “C₃–C₁₀ cycloalkyl group” in the above definition of R⁹ has the samemeaning as indicated hereinbefore for “cycloalkyl group”.

Step B1

Step B1 is a process for the preparation of compounds of general formula(X). Step B1 is accomplished by the selective acylation of one hydroxylgroup of a compound of formula (VIII) using a compound of formula (IX)in the presence of a lipase in the presence or absence of an inertsolvent (preferably in the presence of an inert solvent).

The “lipase” employed in the above reaction is not particularlyrestricted, and the preferred lipase depends on the starting material.Preferred lipases are derived from Pseudomonas sp, Pseudomonasfluorescens, Pseudomonas cepacia, Chromobacterium viscosum, Aspergillusniger, Aspergillus oryzae, Candida antarctica, Candida cylindracea,Candida lipolytica, Candida rugosa, Candida utilis, Penicilliumroqueforti, Rhizopus arrhizus, Rhizopus delemar, Rhizopus javanicus,Rhizomucor miehei, Rhizopus niveus, Humicola lanuginosa, Mucorjavanicus, Mucor miehei, Thermus aquaticus, Thermus flavus, or Thermusthermophilus; or human pancreas, hog pancreas, porcine pancreas, orwheat germ. Partially purified or completely purified enzymes can beused and immobilized enzymes can be also used in the above reaction. Themost preferred lipase is an immobilized Pseudomonas sp. (for example:immobilized lipase from Pseudomonas sp. (product of TOYOBO Co., Ltd.).

The preferred compound of formula (IX) employed in the above reactiondepends on the starting material, and is a vinyl ester of a straightchain aliphatic carboxylic acid such as vinyl n-hexanoate, vinyln-heptanoate, vinyl n-pentanoate, or vinyl acetate; most preferablyvinyl n-hexanoate.

The inert solvent employed in the above reaction is not particularlyrestricted, and the compound of formula (IX) can be used as the solventwithout other solvents. The preferred solvent depends on the startingmaterial, and can be a mixture of various solvents or a solventcontaining water. The preferred solvents include ethers such asdiisopropylether, tert-butyl methyl ether, diethyl ether, ortetrahydrofuran; aliphatic hydrocarbons such as n-hexane or n-pentane;aromatic hydrocarbons such as benzene or toluene; or halogenatedhydrocarbons such as dichloromethane or 1,2-dichloroethane. The morepreferred solvents are ethers, and the most preferred solvents arediisopropyl ether or tert-butyl methyl ether.

The reaction temperature depends on the starting material, solvent,lipase and the like employed in the above reaction and is usuallybetween −50° C. and 50° C., preferably between 0° C. and 40° C.

The reaction time depends on the starting material, solvent, lipase,reaction temperature and the like employed in the above reaction and isusually from 15 minutes to 150 hours, preferably from 30 minutes to 24hours.

Step B2

Step B2 is a process for the preparation of compounds of general formula(XI) and is accomplished by oxidation of the alcohol moiety of acompound of general formula (X) to the corresponding aldehyde moietyusing an oxidizing reagent in an inert solvent.

The oxidation reaction is not particularly restricted provided that itcan convert a primary alcohol into the corresponding aldehyde and, forexample, is the Collins oxidation which is conducted using pyridine andchromic acid in dichloromethane; the PCC oxidation which is conductedusing pyridinium chlorochromate (PPC) in dichloromethane; the PDCoxidation which is conducted using pyridinium dichromate (PDC) indichloromethane; the DMSO oxidation such as the Swern oxidation which isconducted using an electrophilic reagent (for example acetic anhydride,trifluoroacetic anhydride, thionyl chloride, sulfuryl chloride, oxalylchloride, dicyclohexylcarbodiimide, diphenylketene-p-tolylimine,N,N-diethylaminoacetylene, or sulfur trioxide-pyridine complex) anddimethyl sulfoxide (DMSO) in dichloromethane; or the manganese dioxideoxidation which is conducted using manganese dioxide in dichloromethaneor benzene. Preferred oxidation reactions are the PCC oxidation, PDCoxidation or Swern oxidation in dichloromethane.

The reaction temperature depends on the starting material, solvent,oxidizing agent and the like employed in the above reaction and isusually between −78° C. and 80° C., preferably between −78° C. and 30°C.

The reaction time depends on the starting material, solvent, oxidizingagent, reaction temperature and the like employed in the above reactionand is usually from 10 minutes to 48 hours, preferably from 30 minutesto 24 hours.

Step B3

Step B3 is a process for the preparation of compounds of general formula(XIII) and is accomplished by reaction of a compound of formula (XI)with a compound of formula (XII) in the presence of a base in an inertsolvent.

The inert solvent employed in the above reaction is not particularlyrestricted provided that it has no adverse effect on the reaction andcan be, for example, an ether such as diethyl ether, diisopropyl ether,tetrahydrofuran, dioxane, dimethoxyethane, or di (ethylene glycol)dimethyl ether; an aromatic hydrocarbon such as toluene, benzene, orxylene; a halogenated hydrocarbon such as dichloromethane, chloroform,carbon tetrachloride, dichloroethane, chlorobenzene, or dichlorobenzene;a lower alkyl nitrile such as acetonitrile or propionitrile; an amidesuch as formamide, N,N-dimethylformamide, N, N-dimethylacetamide, orhexamethylphosphoric triamide; a lower alkyl alcohol such as methanol,ethanol, propanol or butanol; or water. The solvent is preferably anether (most preferably tetrahydrofuran).

The base employed in the above reaction is not particularly restrictedprovided that it does not change groups other than the aldehyde moietyof the compound of formula (XI) and can be, for example, the same baseas that indicated in Step A2. The base is preferably an alkali metalalkoxide (most preferably potassium tert-butoxide).

The reaction temperature depends on the starting material, solvent, baseand the like employed in the above reaction and is usually between −78°C. and 200° C., preferably between −50° C. and 150° C. (most preferably0° C).

The reaction time depends on the starting material, solvent, base,reaction temperature and the like employed in the above reaction and isusually from 15 minutes to 48 hours (preferably from 30 minutes to8hours).

Step B4

Step B4 is a process for the preparation of compounds of general formula(XIV) and is accomplished by a hydrolysis reaction of a compound offormula (XIII) in the presence of a base in an inert solvent.

The inert solvent employed in the above reaction is not particularlyrestricted provided that it has no adverse effect on the reaction andcan dissolve the starting material to some extent and can be, forexample, an ether such as diethyl ether, diisopropyl ether,tetrahydrofuran, dioxane, dimethoxyethane, or di(ethylene glycol)dimethyl ether; an alcohol such as methanol, ethanol, n-propanol,isopropanol, n-butanol, isobutanol, tert-butanol, isoamyl alcohol,di(ethylene glycol), glycerin, octanol, cyclohexanol, or methylcellosolve; an amide such as formamide, N,N-dimethylformamide,N,N-dimethylacetamide, or hexamethylphosphoric triamide; water; amixture of solvents indicated hereinbefore or a mixture of water and asolvent indicated hereinbefore. The solvent is preferably a mixture ofan alcohol, ether and water or a mixture of an alcohol and water (mostpreferably a mixture of methanol, tetrahydrofuran and water).

The base employed in the above reaction is not particularly restrictedprovided that it does not change groups other than the acyl moiety ofthe compound of formula (XIII) and can be, for example, the same base asthat indicated in Step A2. The base is preferably an alkali metalhydroxide (most preferably sodium hydroxide)

The reaction temperature depends on the starting material, solvent, baseand the like employed in the above reaction and is usually between −78°C. and 150° C., preferably between −50° C. and 100° C. (most preferablynear room temperature).

The reaction time depends on the starting material, base, solvent,reaction temperature and the like employed in the above reaction and isusually from 15 minutes to 48 hours (most preferably from 30 minutes to6 hours).

Step B5

Step B5 is a process for the preparation of compounds of general formula(XV) and is accomplished by treatment of a compound of formula (XIV)with a base in an inert solvent.

The inert solvent employed in the above reaction is not particularlyrestricted provided that it has no adverse effect on the reaction andcan be, for example, an ether such as diethyl ether, diisopropyl ether,tetrahydrofuran, dioxane, dimethoxyethane, or di (ethylene glycol)dimethyl ether; an alcohol such as methanol, ethanol, n-propanol,isopropanol, n-butanol, isobutanol, tert-butanol, isoamyl alcohol,di(ethylene glycol), glycerin, octanol, cyclohexanol, or methylcellosolve; an amide such as formamide, N,N-dimethylformamide,N,N-dimethylacetamide, or hexamethylphosphorictriamide; water; a mixtureof solvents indicated hereinbefore; or a mixture of water and a solventindicated hereinbefore. The solvent is preferably an ether or amide(most preferably tetrahydrofuran).

The base employed in the above reaction is not particularly restrictedprovided that it can be used in general reactions as a base and can be,for example, the same base as that indicated in Step A2. The base ispreferably an alkali metal alkoxide (most preferably potassiumtert-butoxide).

The reaction temperature depends on the starting material, solvent, baseand the like employed in the above reaction and is usually between −78°C. and 150° C., preferably between −50° C. and 100° C., (most preferablybetween 0° C. and room temperature).

The reaction time depends on the starting material, solvent, base,reaction temperature and the like employed in the above reaction and isusually from 15 minutes to 48 hours (preferably from 30 minutes to 8hours).

Step B5 can be also accomplished by reaction with an acylating reagentsuch as N,N-carbonyldiimidazole, dimethyl carbonate, or diethylcarbonate after removal of the protecting group of the amino group ofthe compound of general formula (XIV).

Step B6

Step B6 is a process for the preparation of compounds of general formula(XVI) and is accomplished by reduction of a compound of formula (XV) inthe presence of a reducing agent (preferably by catalytic reductionunder an atmosphere of hydrogen) in an inert solvent.

The inert solvent employed in the above catalytic reduction is notparticularly restricted provided that it has no adverse effect on thereaction and can be, for example, an aliphatic hydrocarbon such ashexane, heptane, ligroin, or petroleum ether; an aromatic hydrocarbonsuch as toluene, benzene, or xylene; a halogenated hydrocarbon such asdichloromethane, chloroform, carbon tetrachloride, dichloroethane,chlorobenzene, or dichlorobenzene, an ester such as methyl acetate,ethyl acetate, propyl acetate, butyl acetate, or diethyl carbonate; anether such as diethyl ether, dioxane, tetrahydrofuran, dimethoxyethane,or di (ethylene glycol) dimethyl ether; an amide such as formamide,N,N-dimethylformamide, N,N-dimethylacetamide, or hexamethylphosphorictriamide; an alcohol such as methanol, ethanol, n-propanol, isopropanol,n-butanol, isobutanol, tert-butanol, isoamyl alcohol, di(ethyleneglycol), glycerin, octanol, cyclohexanol, or methyl cellosolve; anorganic acid such as acetic acid or hydrochloric acid; water; or amixture of water and a solvent indicated hereinbefore. The solvent ispreferably an alcohol or ether (most preferably methanol).

The reducing agent employed in the above catalytic reduction reaction isnot particularly restricted provided that it can be used for generalcatalytic reductions and can be, for example, the same catalyst as thatindicated in Step A3 or Step A4. The catalyst is preferablypalladium-charcoal (most preferably 10% palladium-charcoal).

The pressure of hydrogen is not particularly restricted and is usuallybetween 1 to 10 atmospheric pressures, preferably 1 atmosphericpressure.

The reaction temperature depends on the starting material, solvent,reducing agent and the like employed in the above reaction and isusually between −20° C. and 200° C., preferably between 0° C. and 100°C. (most preferably between 20° C. and 30° C.).

The reaction time depends on the reaction temperature, startingmaterial, reagent, solvent, and the like employed in the above reactionand is usually from 5 minutes to 96 hours, preferably from 15 minutes to24 hours (most preferably from 30 minutes to 2 hours).

Step B7

Step B7 is a process for the preparation of compounds of general formula(XVII), and is accomplished by a hydrolysis reaction of a compound offormula (XVI) in the presence of a base in an inert solvent.

The inert solvent employed in the above reaction is not particularlyrestricted and can be, for example, the same solvent as that indicatedin Step B4. The solvent is preferably a mixture of an alcohol and anether or a mixture of an alcohol and water (most preferably a mixture ofmethanol, tetrahydrofuran and water or a mixture of methanol and water).

The base employed in the above reaction is not particularly restrictedprovided that it has no adverse effect on the hydrolysis reaction, andcan be, for example, the same base as that indicated in Step B4. Thebase is preferably an alkali metal hydroxide (most preferably potassiumhydroxide or sodium hydroxide).

The reaction temperature depends on the starting material, solvent, baseand the like and is usually between −78° C. and 200° C., preferablybetween 0° C. and 180° C. (most preferably between 20° C. and 120° C.).

The reaction time depends on the starting material, base, solvent,reaction temperature, and the like and is usually from 15 minutes to 10days (most preferably from 2 hours to 5 days).

Step B8

If necessary, Step B8 is a process for the preparation of compounds ofgeneral formula (IV) and is accomplished by alkylation or protection ofthe hydroxyl and amino groups of a compound of formula (XVII) in aninert solvent.

The alkylation and protection of the hydroxyl and amino groups can becarried out according to methods known to those skilled in organicchemistry, for example the methods indicated in “Protective Groups inOrganic Synthesis” (Third Edition, 1999, John Wiley & Sons, Inc.), andcan be accomplished by the procedure indicated hereinafter.

The alkylation or protection of the amino group can be accomplished, forexample, by reaction of a compound of formula (XVII) with a compound offormula R¹a-Q (XIX) [wherein R¹a represents a lower alkyl group or aprotecting group of the amino group (which have the same meanings asindicated hereinbefore). Q has the same meaning as indicatedhereinbefore.] in the presence or absence of a base in an inert solvent.

The inert solvent employed in the above reaction is preferably an ethersuch as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane,dimethoxyethane, or di (ethylene glycol) dimethyl ether; or an alcoholsuch as methanol, ethanol, n-propanol, isopropanol, n-butanol,isobutanol, tert-butanol, isoamyl alcohol, di(ethylene glycol),glycerin, octanol, cyclohexanol, or methyl cellosolve.

The base employed in the above reaction is preferably an organic aminesuch as triethylamine, tributylamine, diisopropylethylamine,N-methylmorpholine, or pyridine.

The reaction temperature is between −78° C. and 150° C. (preferablybetween −50° C. and 100° C. and most preferably near room temperature).

The reaction time is usually from 10 minutes to 48 hours (preferablyfrom 20 minutes to 8 hours).

The alkylation or protection of the hydroxyl group can be accomplished,for example, by reaction of a compound of formula (XVII) with a compoundof formula R³a-Q (XX) [wherein R³a represents a lower alkyl group or aprotecting group of the hydroxyl group (which have the same meanings asindicated hereinbefore). Q has the same meaning as indicatedhereinbefore.] in the presence of a base in an inert solvent.

The inert solvent employed in the above reaction is preferably ahalogenated hydrocarbon such as chloroform, dichloromethane,1,2-dichlororethane, or carbon tetrachloride; an amide such asformamide, dimethylformamide, dimethylacetamide, or hexamethylphosphorictriamide; or a sulfoxide such as dimethyl sulfoxide.

The base employed in the above reaction is preferably an alkali metalhydride such as lithium hydride, sodium hydride, or potassium hydride;or an organic amine such as triethylamine, tributylamine,diisopropylethylamine, N-methylmorpholine or pyridine.

The reaction temperature is between −78° C. and 150° C. (preferablybetween −50° C. and 100° C. and most preferably near room temperature).

The reaction time is usually from 10 minutes to 48 hours (preferablyfrom 20 minutes to 8 hours).

The order of the alkylation or protection of the amino and hydroxylgroups can be arbitrarily selected and the reactions can be carried outin order of precedence.

After the reactions in Method B, the desired compound in each Step canbe isolated from the reaction mixture by conventional treatments, forexample, neutralization of the reaction mixture, if necessary, orfiltration of the reaction mixture, when insoluble material is presentin the reaction mixture, addition of a solvent immiscible with watersuch as ethyl acetate to the neutralized solution or the filtrate,washing the resulting organic layer with water, separation of theorganic layer containing the desired product, drying of the organiclayer over anhydrous magnesium sulfate, anhydrous sodium sulfate or thelike, and then evaporation of the organic solvent to give the desiredproduct. If necessary, the product thus obtained is further purified byconventional treatments, for example by recrystallization orreprecipitation, or by conventional procedures in organic chemistry, forexample, absorption column chromatography using a carrier such as silicagel, alumina, or Florisil consisting of magnesium and silica gel;partition column chromatography using a synthetic absorbent such asSephadex LH-20 (product of Pharmacia Co., Ltd), Amberlite XAD-11(product of Rohm & Hass Co., Ltd), or Diaion HP-20 (product ofMitsubishi Chemicals Co., Ltd.); ion exchange chromatography; normalphase or reversed phase column chromatography using silica gel oralkylated silica gel (preferably high performance liquid columnchromatography); or an appropriate combination of these chromatographictechniques and elution using an appropriate solvent to isolate andpurify the desired product.

In addition, if it is necessary to separate isomers, which are obtainedin each Step of method B, each isomer can be isolated according to theisolation or purification procedures indicated hereinbefore after thereaction of each step in method B, or after protection of the hydroxyland/or amino groups in method B.

The starting materials of formula (VIII) and (IX) are known or can beprepared according to similar procedures to those known to those skilledin the art [starting material of formula (VIII) J. Org. Chem., 64, 8220(1999)].

(Method C)

Method C is a process for the preparation of compounds of generalformula (XII).

In the above reaction scheme R⁶, R⁷, X, m, Q and Ph have the samemeanings as those indicated hereinbefore.

Step C1

Step C1 is a process for the preparation of compounds of general formula(XII) and is accomplished by reaction of a compound of general formula(XVIII) with triphenylphosphine in an inert solvent.

The inert solvent employed in the above reaction is not particularlyrestricted provided that it has no adverse effect on the reaction andcan be, for example, an aliphatic hydrocarbon such as hexane, heptane,ligroin, or petroleum ether; an aromatic hydrocarbon such as toluene,benzene, or xylene; a halogenated hydrocarbon such as dichloromethane,chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, ordichlorobenzene; an ether such as diethyl ether, diisopropyl ether,tetrahydrofuran, dioxane, dimethoxyethane, or di(ethylene glycol)dimethyl ether; a lower alkyl nitrile such as acetonitrile orpropionitrile; a lower alkyl alcohol such as methanol, ethanol,propanol, or butanol; or a lower alkyl ketone such as acetone or methylethyl ketone. The solvent is preferably an ether or nitrile.

The reaction temperature depends on the starting material, solvent andthe like and is usually between −10° C. and 200° C., preferably between0° C. and 150° C. (most preferably between 20° C. and 120° C.).

The reaction time depends on the reaction temperature, startingmaterial, and solvent employed in the above reaction and is usually from5 minutes to 96 hours, preferably from 15 minutes to 48 hours (mostpreferably from 1 hour to 8 hours).

The desired product of formula (XII) of Step C1, if necessary, can beisolated or purified by conventional procedures, for example,recrystallization or reprecipitation, or by conventional proceduresknown to those skilled in organic chemistry, for example, absorptioncolumn chromatography using a carrier such as silica gel, alumina, orFlorisil consisting of magnesium and silica gel; partition columnchromatography using a synthetic absorbent such as Sephadex LH-20(product of Pharmacia Co., Ltd), Amberlite XAD-11 (product of Rohm &Hass Co., Ltd), or Diaion HP-20 (product of Mitsubishi Chemicals Co.,Ltd.); ion exchange chromatography; normal phase or reversed phasecolumn chromatography using silica gel or alkylated silica gel(preferably high performance liquid column chromatography); or anappropriate combination of these chromatographic techniques; and elutionusing an appropriate solvent.

In addition, if it is necessary to separate isomers, which are obtainedin Step C1, each isomer can be isolated according to the isolation orpurification procedures indicated hereinbefore after the reaction ofStep C1.

The starting material of formula (XVIII) is known or can be preparedaccording to a similar procedure to those known to those skilled in theart [X=O: J. Am. Chem. Soc., 49, 1066 (1927), X=N-Me : J. Org. Chem.,52, 19 (1987)].

(Method D)

Method D is a process for increasing the optical purity of compounds ofgeneral formula (XVII).

In the above reaction scheme R⁴, R⁶, R⁷, X and m have the same meaningsas those indicated hereinbefore.

Step D1

Step D1 is a process for increasing the optical purity of compounds offormula (XVII). Step D1 is carried out by treatment of a compound offormula (XVII) with an optically active organic acid in an inert solventto form a salt of the compound of formula (XVII), if necessary, withrecrystallization of the salt in order to increase the optical purity,followed by treatment of the salt with a base to regenerate the freeform of the compound of general formula (XVII).

The inert solvent employed in the above reaction is not particularlyrestricted provided that it has no adverse effect on the reaction and,for example, is an aliphatic hydrocarbon such as hexane, heptane,ligroin, or petroleum ether; an aromatic hydrocarbon such as toluene,benzene, or xylene; a halogenated hydrocarbon such as dichloromethane,chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, ordichlorobenzene; an ester such as methyl acetate, ethyl acetate, propylacetate, butyl acetate, or diethyl carbonate; an ether such as diethylether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, ordi(ethylene glycol) dimethyl ether; an alcohol such as methanol,ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol,isoamyl alcohol, di(ethylene glycol), glycerin, octanol, cyclohexanol,or methyl cellosolve; a nitrile such as acetonitrile or propionitrile;water; or a mixture of water and a solvent indicated hereinbefore. Theinert solvent is preferably an alcohol (most preferably methanol orethanol) or a mixture of water and an alcohol.

The optically active organic acid employed in the above reaction is notparticularly restricted and is, for example, tartaric acid, mandelicacid or 10-camphorsulfonic acid. The preferred acid is tartaric acid.

The process for regeneration of the compound of formula (XVII) as a freeform from the salt can be easily accomplished by a normal extractionprocedure using an organic solvent and a base.

After the reaction, each desired compound of Method D can be isolatedfrom the reaction mixture by conventional treatments, for example,neutralization of the reaction mixture, if necessary, or filtration ofthe reaction mixture when insoluble material is present in the reactionmixture, addition of a solvent immiscible with water such as ethylacetate to the neutralized solution or the filtrate, washing theresulting organic layer with water, separation of the organic layercontaining the desired product, drying of the organic layer overanhydrous magnesium sulfate, anhydrous sodium sulfate or the like, andthen evaporation of the organic solvent to give the desired product. Theproduct thus obtained, if necessary, is further purified by conventionaltreatments, for example by recrystallization or reprecipitation, or byconventional procedures in organic chemistry, for example, absorptioncolumn chromatography using a carrier such as silica gel, alumina, orFlorisil consisting of magnesium and silica gel; partition columnchromatography using a synthetic absorbent such as Sephadex LH-20(product of Pharmacia Co., Ltd), Amberlite XAD-11 (product of Rohm &Hass Co., Ltd), or Diaion HP-20 (product of Mitsubishi Chemicals Co.,Ltd.); ion exchange chromatography; normal phase or reversed phasecolumn chromatography using silica gel or alkylated silica gel(preferably high performance liquid column chromatography); or anappropriate combination of these chromatographic techniques; and elutionusing an appropriate solvent to isolate and purify the desired product.

(Method E)

Method E is a process for the preparation of compounds of generalformula (XXIV). Method E is a particularly useful method for thepreparation of compounds of Method C, wherein X is N-D and m is 0.Method E can be accomplished according to similar procedures to thoseindicated in the literature (J. Org. Chem., 52, 19 (1987)).

In the above reaction scheme D, R⁶, R⁷ and Q have the same meanings asthose indicated hereinbefore.

Step E1

Step E1 is a process for the preparation of compounds of general formula(XXII). Step E1 is accomplished by reaction of a compound of formula(XXI) with formalin and dimethylamine hydrochloride according to similarprocedures to those indicated in the literature (for example, J. Am.Chem. Soc., 73, 4921 (1951) or the like).

Step E2

Step E2 is a process for the preparation of compounds of general formula(XXIII). Step E2 is accomplished by reaction of a compound of formula(XXII) with a methyl halide such as methyl iodide or the like to give aquaternary salt.

The inert solvent employed in the above reaction is hot particularlyrestricted provided that it has no adverse effect on the reaction and,for example, can be an aliphatic hydrocarbon such as hexane, heptane,ligroin, or petroleum ether; an aromatic hydrocarbon such as toluene,benzene, or xylene; a halogenated hydrocarbon such as dichloromethane,chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, ordichlorobenzene; an ether such as diethyl ether, diisopropyl ether,tetrahydrofuran, dioxane, dimethoxyethane, or di(ethylene glycol)dimethyl ether; a lower alkyl nitrile such as acetonitrile orpropionitrile; a lower alkyl alcohol such as methanol, ethanol,propanol, or butanol; or a lower alkyl ketone such as acetone or methylethyl ketone. The inert solvent is preferably an alcohol.

The reaction temperature depends on the starting material, solvent andthe like and is usually between −10° C. and 200° C., preferably between0° C. and 50° C.

The reaction time depends on the reaction temperature, starting materialand solvent employed in the above reaction and is generally from 5minutes to 96 hours, preferably from 15 minutes to 48 hours (mostpreferably from 1 hour to 8 hours).

Step E3

Step E3 is a process for the preparation of compounds of general formula(XXIV). Step E3 is accomplished by reaction of a compound of generalformula (XXIII) with triphenylphosphine in an inert solvent.

The inert solvent employed in the above reaction is not particularlyrestricted provided that it has no adverse effect on the reaction and,for example, can be an aliphatic hydrocarbon such as hexane, heptane,ligroin, or petroleum ether; an aromatic hydrocarbon such as toluene,benzene, or xylene; a halogenated hydrocarbon such as dichloromethane,chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, ordichlorobenzene; an ether such as diethyl ether, diisopropyl ether,tetrahydrofuran, dioxane, dimethoxyethane, or di(ethylene glycol)dimethyl ether; a lower alkyl nitrile such as acetonitrile orpropionitrile; a lower alkyl alcohol such as methanol; ethanol,propanol, or butanol; or a lower alkyl ketone such as acetone or methylethyl ketone. The inert solvent is preferably an ether or nitrile (mostpreferably acetonitrile)

The reaction temperature depends on the starting material, solvent andthe like and is usually between room temperature and 200° C., preferablybetween 0° C. and 150° C. (most preferably between 20° C. and 100° C.).

The reaction time depends on the reaction temperature, starting materialand solvent employed in the above reaction and is generally from 5minutes to 96 hours, preferably from 15 minutes to 48 hours (mostpreferably from 1 hour to 8 hours).

After the reaction, each desired compound of Method E can be isolatedfrom the reaction mixture by conventional treatments, for example,neutralization of the reaction mixture, if necessary, or filtration ofthe reaction mixture when insoluble material is present in the reactionmixture, addition of a solvent immiscible with water such as ethylacetate to the neutralized solution or the filtrate, washing theresulting organic layer with water, separation of the organic layercontaining the desired product, drying of the organic layer overanhydrous magnesium sulfate, anhydrous sodium sulfate or the like, andthen evaporation of the organic solvent to give the desired product. Theproduct thus obtained, if necessary, is further purified by conventionaltreatments, for example recrystallization or reprecipitation, or byconventional procedures in organic chemistry, for example, absorptioncolumn chromatography using a carrier such as silica gel, alumina, orFlorisil consisting of magnesium and silica gel; partition columnchromatography using a synthetic absorbent such as Sephadex LH-20(product of Pharmacia Co., Ltd), Amberlite XAD-11 (product of Rohm &Hass Co., Ltd), or Diaion HP-20 (product of Mitsubishi Chemicals Co.,Ltd.); ion exchange chromatography; normal phase or reversed phasecolumn chromatography using silica gel or alkylated silica gel(preferably high performance liquid column chromatography); or anappropriate combination of these chromatographic techniques; and elutionusing an appropriate solvent to isolate and purify the desired product.

In addition, if it is necessary to separate isomers, which are obtainedin each step of method E, each isomer can be isolated according to theisolation or purification procedures indicated hereinbefore after thereaction of each step in method E, or after removal of the protectinggroup in each step in method E.

The starting material of formula (XXI) is known or can be preparedaccording to similar procedures to those known to those skilled in theart.

(Method F)

Method F is a process for the preparation of compounds of generalformula (XXVIII) from compounds of general formula (XVI) or (IV). MethodF is an alternative process to Method A.

In the above reaction scheme, R¹, R², R³, R⁴, R⁵, R⁶, R⁷, D, Q, Z, and mhave the same meanings as those indicated hereinbefore.

Step F1

Step F1 is a process for the preparation of compounds of general formula(XXVI) or (XXVII). Step F1 is accomplished by reaction of a compound ofgeneral formula (XVI) or (IV) with an acyl halide of general formula(XXV) in the presence of a base in an inert solvent.

The inert solvent employed in the above reaction is not particularlyrestricted and can be, for example, an aliphatic hydrocarbon such ashexane, heptane, ligroin, or petroleum ether; an aromatic hydrocarbonsuch as toluene, benzene, or xylene; a halogenated hydrocarbon such asdichloromethane, chloroform, carbon tetrachloride, dichloroethane,chlorobenzene, or dichlorobenzene; an ether such as diethyl ether,diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, ordi(ethylene glycol) dimethyl ether; a lower alkyl nitrile such asacetonitrile or propionitrile; a lower alkyl alcohol such as methanol,ethanol, propanol, or butanol; or a lower alkyl ketone such as acetoneor methyl ethyl ketone. The solvent is preferably an aromatichydrocarbon (particularly preferably benzene, toluene or xylene).

The base employed in the above reaction is not particularly restrictedprovided that it activates the compound of formula (XXV) and is, forexample, 4-(N,N-dimethylaminopyridine) or 4-pyrrolidinopyridine.

The reaction temperature depends on the starting material, solvent, baseand the like and is usually between 0° C. and 200° C., preferablybetween room temperature and 150° C.

The reaction time depends on the starting material, base, solvent,reaction temperature and the like and is usually from 15 minutes to 7days, preferably from 6 hours to 3 days.

Step F2

Step F2 is a process for the preparation of compounds of general formula(XXVIII). Step F2 is accomplished by a hydrolysis reaction of a compoundof formula (XXVI) or (XXVII) in the presence of a base in an inertsolvent according to a similar procedure to that indicated in Step B7.

After the reaction, each desired compound of Method F can be isolatedfrom the reaction mixture by conventional treatments, for example,neutralization of the reaction mixture, if necessary, or filtration ofthe reaction mixture when insoluble material is present in the reactionmixture, addition of a solvent immiscible with water such as ethylacetate to the neutralized solution, washing the resulting organic layerwith water, separation of the organic layer containing the desiredproduct, drying of the organic layer over anhydrous magnesium sulfate,anhydrous sodium sulfate or the like, and then evaporation of theorganic solvent to give the desired product. The product thus obtained,if necessary, is further purified by conventional treatments, forexample recrystallization or reprecipitation, or by conventionalprocedures in organic chemistry, for example, absorption columnchromatography using a carrier such as silica gel, alumina, or Florisilconsisting of magnesium and silica gel; partition column chromatographyusing a synthetic absorbent such as Sephadex LH-20 (product of PharmaciaCo., Ltd.), Amberlite XAD-11 (product of Rohm & Hass Co., Ltd.), orDiaion HP-20 (product of Mitsubishi Chemicals Co., Ltd.); ion exchangechromatography; normal phase or reversed phase column chromatographyusing silica gel or alkylated silica gel (preferably high performanceliquid column chromatography); or an appropriate combination of thesechromatographic techniques; and elution using an appropriate solvent toisolate and purify the desired product.

In addition, if it is necessary to separate isomers, which are obtainedin each step of method F, each isomer can be isolated according to theisolation or purification procedures indicated hereinbefore after thereaction of each step in method F, or after removal of the protectinggroup in method F.

(Method G)

Method G is a process for the preparation of compounds of generalformula (XXVIII) from compounds of formula (XVI) or (IV) and is analternative process to method F.

In the above reaction scheme R¹, R², R³, R⁴, R⁵, R⁶, R⁷, D, Z and m havethe same meanings as those indicated hereinbefore.

Step G1

Step G1 is a process for the preparation of compounds of general formula(XXX) or (XXXI). Step G1 is accomplished by reaction of a compound ofgeneral formula (XVI) or (IV) with an amide derivative of formula (XXIX)in the presence of phosphorous oxychloride or oxalyl chloride in aninert solvent according to similar procedures to those indicated in theliterature (for example J. Med. Chem., 40, 3381 (1997)).

The inert solvent employed in the above reaction is not particularlyrestricted and can be an aliphatic hydrocarbon such as hexane, heptane,ligroin, or petroleum ether; an aromatic hydrocarbon such as toluene,benzene, or xylene; a halogenated hydrocarbon such as dichloromethane,chloroform, carbon tetrachloride, dichloroethane, chlorobenzene,ordichlorobenzene; an ether such as diethyl ether, diisopropyl ether,tetrahydrofuran, dioxane, dimethoxyethane, or di(ethylene glycol)dimethyl ether; a lower alkyl nitrile such as acetonitrile orpropionitrile; a lower alkyl alcohol such as methanol, ethanol,propanol, or butanol; or a lower alkyl ketone such as acetone or methylethyl ketone. The inert solvent is preferably an aromatic hydrocarbon(particularly preferably benzene or toluene).

The reaction temperature depends on the starting material, solvent, baseand the like and is usually between 0° C. and 200° C., preferablybetween room temperature and 150° C.

The reaction time depends on the starting material, base, solvent,reaction temperature, and the like and is generally from 15 minutes to 7days, preferably from 6 hours to 3 days.

Step G2

Step G2 is a process for the preparation of compounds of general formula(XXVIII). Step G2 is accomplished by a hydrolysis reaction of a compoundof formula (XXX) or (XXXI) in the presence of a base in an inert solventaccording to a similar procedure to that indicated in Step B7.

After the reaction, each desired compound of Method G can be isolatedfrom the reaction mixture by conventional treatments, for example,neutralization of the reaction mixture, if necessary, or filtration ofthe reaction mixture when insoluble material is present in the reactionmixture, addition of a solvent immiscible with water such as ethylacetate to the neutralized solution or the filtrate, washing theresulting organic layer with water, separation of the organic layercontaining the desired product, drying of the organic layer overanhydrous magnesium sulfate, anhydrous sodium sulfate or the like, andthen evaporation of the organic solvent to give the desired product. Theproduct thus obtained, if necessary, is further purified by conventionaltreatments, for example recrystallization or reprecipitation, or byconventional procedures in organic chemistry, for example, absorptioncolumn chromatography using a carrier such as silica gel, alumina, orFlorisil consisting of magnesium and silica gel; partition columnchromatography using a synthetic absorbent such as Sephadex LH-20(product of Pharmacia Co., Ltd.), Amberlite XAD-11 (product of Rohm &Hass Co., Ltd.), or Diaion HP-20 (product of Mitsubishi Chemicals Co.,Ltd.); ion exchange chromatography; normal phase or reversed phasecolumn chromatography using silica gel or alkylated silica gel(preferably high performance liquid column chromatography); or anappropriate combination of these chromatographic techniques; and elutionusing an appropriate solvent to isolate and purify the desired product.

In addition, if it is necessary to separate isomers, which are obtainedin each step of method G, each isomer can be isolated according to theisolation or purification procedures indicated hereinbefore after thereaction of each step in method G, or after removal of the protectinggroup in method G.

(Method H)

Method H is a process for the preparation of compounds of generalformula (XXVIII) from compounds of formula (XVI) or (IV) and is analternative process to method F.

In the above reaction scheme R¹, R², R³, R⁴, R⁵, R⁶, R⁷, D, Q, Z and mhave the same meanings as those indicated hereinbefore.

Step H1

Step H1 is a process for the preparation of compounds of general formula(XXX) or (XXXI). Step H1 is accomplished by a Friedel-Crafts reaction ofa compound of general formula (XVI) or (IV) with an acid halide offormula (XXV) in the presence of a Lewis acid such as aluminum chloridein an inert solvent according to similar procedures to those indicatedin the literature (for example Synth. Commun., 19, 2721 (1989)). Step H1can be also accomplished by treatment of a compound of general formula(XVI) or (IV) with a Grignard reagent, followed by reaction with an acidhalide of formula (XXV) in an inert solvent according to similarprocedures to those indicated in the literature (for example Bioorg.Med. Chem., 9, 621 (2001)).

The inert solvent employed in the above reaction is not particularlyrestricted and, for example, can be an aliphatic hydrocarbon such ashexane, heptane, ligroin, or petroleum ether; an aromatic hydrocarbonsuch as toluene, benzene, or xylene; a halogenated hydrocarbon such asdichloromethane, chloroform, carbon tetrachloride, dichloroethane,chlorobenzene, or dichlorobenzene; an ether such as diethyl ether,diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, ordi(ethylene glycol) dimethyl ether; or a lower alkyl ketone such asacetone or methyl ethyl ketone. The inert solvent employed in theFriedel-Crafts reaction is preferably a halogenated hydrocarbon(particularly preferably dichloromethane or dichloroethane). The inertsolvent employed in the Grignard reaction is preferably an ether(particularly preferably diethyl ether or tetrahydrofuran).

The reaction temperature depends on the starting material, solvent,reagent and the like and is usually between 0° C. and 100° C.,preferably between 0° C. and 50° C.

The reaction time depends on the starting material, base, solvent,reaction temperature, and the like and is generally from 15 minutes to24 hours, preferably from 1 hour to 12 hours.

Step H2

Step H2 is a process for the preparation of compounds of general formula(XXVIII). Step H2 is accomplished by a hydrolysis reaction of a compoundof formula (XXX) or (XXXI) in the presence of a base in an inert solventaccording to the same procedure as that indicated in Step G2.

After the reaction, each desired compound of Method H can be isolatedfrom the reaction mixture by conventional treatments, for example,neutralization of the reaction mixture, if necessary, or filtration ofthe reaction mixture when insoluble material is present in the reactionmixture, addition of a solvent immiscible with water such as ethylacetate to the neutralized solution or the filtrate, washing theresulting organic layer with water, separation of the organic layercontaining the desired product, drying of the organic layer overanhydrous magnesium sulfate, anhydrous sodium sulfate or the like, andthen evaporation of the organic solvent to give the desired product. Theproduct thus obtained, if necessary, is further purified by conventionaltreatments, for example recrystallization or reprecipitation, or byconventional procedures in organic chemistry, for example, absorptioncolumn chromatography using a carrier such as silica gel, alumina, orFlorisil consisting of magnesium and silica gel; partition columnchromatography using a synthetic absorbent such as Sephadex LH-20(product of Pharmacia Co., Ltd.), Amberlite XAD-11 (product of Rohm &Hass Co., Ltd.), or Diaion HP-20 (product of Mitsubishi Chemicals Co.,Ltd.); ion exchange chromatography; normal phase or reversed phasecolumn chromatography using silica gel or alkylated silica gel(preferably high performance liquid column chromatography); or anappropriate combination of these chromatographic techniques; and elutionusing an appropriate solvent to isolate and purify the desired product.

In addition, if it is necessary to separate isomers, which are obtainedin each step of method H, each isomer can be isolated according to theisolation or purification procedures indicated hereinbefore after thereaction of each step in the method H, or after removal of theprotecting group in method H.

(Method I)

Compounds of formula (II) can be prepared by methods appropriatelyselected from Methods A to H indicated hereinbefore, and can be alsoproduced by Method I described hereinafter.

In the above reaction scheme R¹, R², R⁴, R⁵, R⁶, R⁷, R¹⁰, R¹¹, X, Y, Zand n have the same meanings as those indicated hereinbefore. R^(1a),R^(2a), R^(4a), R^(5a), R^(6a), R^(7a), Y^(a), and Z^(a) have the samemeanings as R¹, R², R⁴, R⁵, R⁶, R⁷, Y, and Z respectively, and whenR^(1a), R^(2a), R^(4a), R^(5a), R^(6a), R^(7a), Y^(a), and Z^(a) haveone or more hydroxyl, amino and/or carboxyl groups, R^(1a), R^(2a),R^(4a), R^(5a), R^(6a), R^(7a), Y^(a), and Z^(a) represent groups whichmay optionally contain one or more protected hydroxyl, amino and/orcarboxyl groups. R¹² and R¹³ are the same or different and eachrepresents a lower alkyl group (preferably an ethyl or isopropyl group).

Step I1

Step I1 is a process for the preparation of compounds of general formula(II). Step I1 is accomplished by reaction of an alcohol derivative offormula (I′), which is a compound of formula (I) (R³ is a hydrogenatom), with a compound of formula (XXXII), to afford an ester derivativeof phosphorous acid, followed by reaction with an oxidizing agent and,if necessary, removal of one or more protecting groups of the amino,hydroxyl, carboxyl and/or phosphoric acid groups.

The removal of the protecting groups of the hydroxyl, amino and/orcarboxyl groups of R¹, R², R⁴, R⁵, R⁶, R⁷, Y, and Z is accomplishedaccording to the same procedures as those indicated in Step A7.

The order of the removal reactions of the protecting groups of theamino, hydroxyl and/or carboxyl groups can be arbitrarily selected andthe removal reactions of these groups can be preferentially carried outaccording to the appropriate reaction conditions.

The esterification of phosphoric acid with a compound having a primaryhydroxyl group can be easily accomplished by procedures known to thoseskilled in organic chemistry (for example, Jikken Kagaku Koza 22 (4^(th)Edition) “Organic Synthesis IV” Chapter 3 “Ester of Phosphoric Acid”(published Maruzen Co., Ltd.)). The preferred procedure will be shownhereinafter.

The process is carried out by reaction of an alcohol derivative offormula (I′) with a compound of formula (XXXII) in the presence of anactivating reagent in an inert solvent to afford an ester of phosphorousacid, followed by reaction with an oxidizing reagent.

The inert solvent employed in the reaction of the compound of formula(I′) with the compound of formula (XXXII) is, for example, an aliphatichydrocarbon such as hexane or heptane; an aromatic hydrocarbon such asbenzene, toluene, or xylene; a halogenated hydrocarbon such asdichloromethane, chloroform, 1,2-dichloroethane, or carbontetrachloride; an ether such as diethyl ether, diisopropyl ether, ortetrahydrofuran; or a mixture of the solvents indicated hereinbefore.The inert solvent is preferably a halogenated hydrocarbon or ether (mostpreferably dichloromethane or tetrahydrofuran).

The activating reagent employed in the above reaction is, for example, atetrazole derivative such as 1H-tetrazole, 5-methyl-1H-tetrazole, or5-phenyl-1H-tetrazole (preferably 1H-tetrazole).

The compound of formula (XXXII) is preferably a phosphoramidite such asdiallyl N,N-diisopropylphosphoramidite, dimethylN,N-diisopropylphosphoramidite, diethyl N,N-diisopropylphosphoramidite,di-tert-butyl N,N-diisopropylphosphoramidite, dibenzylN,N-diisopropylphosphoramidite, dimethyl N,N-diethylphosphoramidite,di-tert-butyl N,N-diethylphosphoramidite, dibenzylN,N-diethylphosphoramidite,N,N-diethyl-1,5-dihydro-2,4,3-benzodioxaphosphepin-3-amine,bis(2-cyanoethyl) N,N-diisopropylphosphoramidite, orbis(9-fluorenylmethyl) N,N-diisopropylphosphoramidite, most preferablydiallyl N,N-diisopropylphosphoramidite.

The reaction temperature depends on the starting material, solvent andthe like and is usually between −10° C. and 60° C. (preferably between0° C. and 30° C.)

The reaction time depends on the starting material, solvent, reactiontemperature, and the like and is generally from 10 minutes to 24 hours(preferably from 30 minutes to 2 hours).

The ester of phosphorous acid thus obtained in the above reaction can beused in next oxidation reaction without isolation or purification.

The inert solvent employed in the oxidation is the same solvent as thatindicated for the reaction of the alcohol derivative of formula (I′)with the compound of formula (XXXII).

The oxidizing agent is, for example, a peroxide such as tert-butylhydroperoxide, cumene hydroperoxide, m-chloroperbenzoic acid,3,5-dinitroperbenzoic acid, o-carboxyperbenzoic acid, dimethyloxolane,peracetic acid, trifluoroperacetic acid, perphthalic acid, or hydrogenperoxide, preferably tert-butyl hydroperoxide or m-chloroperbenzoicacid.

The reaction temperature depends on the ester of phosphorous acid,oxidizing agent, solvent and the like and is usually between −78° C. androom temperature (preferably between −78° C. and 0° C.).

The reaction time depends on the ester of phosphorous acid, oxidizingagent, solvent, reaction temperature, and the like and is generally from5 minutes to 2 hours (preferably from 5 minutes to 30 minutes).

When the protecting group of phosphoric acid is a lower alkyl groupwhich may be optionally substituted with one or more cyano, optionallysubstituted silyl, aryl, heterocyclyl, arylthio, or sulfonyl groups orhalogen atoms, said protecting group can be removed by acid hydrolysisin the presence of water in an inert solvent or by reaction with atrimethylsilyl halide (for example, trimethylsilyl bromide ortrimethylsilyl iodide) in an inert solvent.

The inert solvent employed in the above hydrolysis reaction is, forexample, an alcohol such as methanol or ethanol; or an ether such asdiethyl ether, diisopropyl ether, tetrahydrofuran, or dioxane;preferably an ether and most preferably dioxane.

The acid employed in the above reaction is, for example, an inorganicacid such as hydrochloric acid, sulfuric acid, phosphoric acid, ornitric acid; preferably hydrochloric acid.

The reaction temperature is between 0° C. and 150° C. (preferablybetween 20° C. and 100° C.).

The reaction time is from 1 hour to 60 hours (preferably from 1 hour to48 hours).

The inert solvent employed in the reaction with a trimethylsilyl halideis, for example, an aliphatic hydrocarbon such as hexane or heptane; anaromatic hydrocarbon such as benzene, toluene or xylene; a halogenatedhydrocarbon such as dichloromethane, chloroform, 1,2-dichloroethane, orcarbon tetrachloride; a nitrile such as acetonitrile, or a mixture ofthe solvents indicated hereinbefore. The solvent is preferably ahalogenated hydrocarbon or a nitrile (more preferably chloroform,dichloromethane or acetonitrile).

The reaction temperature depends on the starting material, solvent andthe like employed in the above reaction and is generally between −78° C.and 100° C. (preferably between 0° C. and 80° C.).

The reaction time depends on the starting material, solvent, reactiontemperature, and the like employed in the above reaction and isgenerally from 10 minutes to 24 hours (preferably from 1 hour to 6hours).

When the protecting group of phosphoric acid is a lower alkenyl group,said protecting group can be removed by reaction with a palladiumcompound in the presence of an amine, formic acid, a salt of formicacid, a trialkyltin compound or a compound having an active methylenegroup in an inert solvent.

The inert solvent employed in the above reaction is, for example, analiphatic hydrocarbon such as hexane or heptane; an aromatic hydrocarbonsuch as toluene, benzene, or xylene; a, halogenated hydrocarbon such aschloroform or dichloromethane; a nitrile such as acetonitrile; an estersuch as methyl acetate, ethyl acetate, or propyl acetate; an ether suchas diethyl ether, diisopropyl ether, tetrahydrofuran or dioxane; analcohol such as methanol, ethanol, n-propanol, or isopropanol; anorganic acid such as acetic acid; water; or a mixture of water and asolvent indicated hereinbefore. The solvent is preferably a nitrile oran ether (particularly preferably acetonitrile or tetrahydrofuran).

The amine employed in the above reaction is, for example, a tertiaryamine such as triethylamine, tributylamine, diisopropylethylamine,N-methylmorpholine, 1,4-diazabicyclo[2.2.2]octane (DABCO); a secondaryamine such as diethylamine, dimethylamine, diisopropylamine, orpyrrolidine; or a primary amine such as ethylamine, propylamine,butylamine, N-N-dimethylaniline, or N,N-diethylaniline. The preferredamine is pyrrolidine.

The salt of formic acid employed in the above reaction is preferably theammonium salt of formic acid, the triethylamine salt of formic acid, orthe n-butylamine salt of formic acid.

The trialkyltin compound employed in the above reaction is preferablytrimethyltin, triethyltin or tributyltin and particularly preferablytributyltin.

The compound having an active methylene group employed in the abovereaction is, for example, an ester of malonic acid such as methylmalonate or ethyl malonate; an ester of cyanoacetic acid such as methylcyanoacetate; an ester of a β-ketoacetic acid such as methylacetoacetate, ethyl acetoacetate, or ethyl benzoate; a 1,3-diketone suchas acetylacetone, benzoylacetone, dibenzoylmethane,1,3-cyclopentanedione, 1,3-cyclohexanedione, or dimedone; or an alkalimetal salt of a compound having an active methylene group indicatedhereinbefore. The compound is preferably a sodium salt of a 1,3-diketoneor an ester of malonic acid.

The palladium compound employed in the above reaction is, for example, apalladium compound such as tetrakis(triphenylphosphine)palladium,diacetoxypalladium, dichlorodi(triphenylphosphine)palladium, orbis(dibenzylideneacetone)palladium. The preferred palladium compound istetrakis(triphenylphosphine)palladium.

The reaction temperature depends on the starting material, solvent andthe like employed in the reaction and is generally between 0° C. and100° C. (preferably between 20° C. and 80° C.).

The reaction time depends on the starting material, solvent, reactiontemperature, and the like employed in the reaction and is generally from10 minutes to 48 hours (preferably from 30 minutes to 24 hours).

When the protecting group of phosphoric acid is an arylmethyl group,said group is removed by the same procedure as that described in thecase where the protecting group of the amino group is an aralkyl oraralkyloxycarbonyl group in Step A7 indicated hereinbefore.

When the protecting group of phosphoric acid is an aryl group, saidgroup is removed by the same procedure as that described in the casewhere the protecting group of the amino group is a lower aliphatic acylgroup, an aromatic acyl group, a lower alkoxycarbonyl group or asubstituted methylene group which can form a Schiff base group in StepA7 indicated hereinbefore.

When the protecting group of phosphoric acid is an amide group, saidgroup is removed by the same acid treatment as that described in thecase where the protecting group of the amino group is an aliphatic acylgroup, an aromatic acyl group, an alkoxycarbonyl group or a substitutedmethylene group which can form a Schiff base in Step A7 indicatedhereinbefore.

After the reaction, the desired compound of each reaction can beisolated from the reaction mixture by conventional treatments, forexample, if necessary, neutralization of the reaction mixture; ordecomposition of the oxidizing agent with a reducing agent if theoxidizing agent is present in the reaction mixture, or filtration of thereaction mixture when insoluble material is present in the reactionmixture, addition of a solvent immiscible with water such as ethylacetate to the neutralized solution or the filtrate, separation of theorganic layer containing the desired compound, washing the resultingorganic layer with water, drying of the organic layer over anhydrousmagnesium sulfate, anhydrous sodium sulfate, anhydrous sodiumhydrogencarbonate or the like, and then evaporation of the organicsolvent to give the desired product. The product thus obtained, ifnecessary, is further purified by conventional procedures in organicchemistry, for example by recrystallization, reprecipitation,chromatography or an appropriate combination of these isolation orpurification procedures.

(Method J)

Compounds of formula (III) can be produced by methods appropriatelyselected from Methods A to H, and also can be prepared by Method Jindicated hereinafter.

In the above reaction scheme R¹, R^(1a), R², R^(2a), R⁴, R^(4a), R⁵,R^(5a), R⁶, R^(6a), R⁷, R^(7a), R¹⁰, R¹¹, Y, Y^(a), Z, Z^(a) and n havethe same meanings as those indicated hereinbefore.

Step J1

Step J1 is a process for the preparation of aldehyde compounds ofgeneral formula (XXXIII) and is accomplished by oxidation of an alcoholcompound of general formula (I′).

The oxidation reaction is not particularly restricted provided that itcan convert a primary alcohol into the corresponding aldehyde and, forexample, is the Collins oxidation which is conducted using pyridine andchromic acid in dichloromethane; the PCC oxidation which is conductedusing pyridinium chlorochromate (PPC) in dichloromethane; the PDCoxidation which is conducted using pyridinium dichromate (PDC) indichloromethane; the DMSO oxidation such as the Swern oxidation which isconducted using an electrophilic reagent (for example acetic anhydride,trifluoroacetic anhydride, thionyl chloride, sulfuryl chloride, oxalylchloride, dicyclohexylcarbodiimide, diphenylketene-p-tolylimine,N,N-diethylaminoacetylene, or sulfur trioxide-pyridine complex) anddimethyl sulfoxide (DMSO) in dichloromethane; the manganese dioxideoxidation which is conducted using manganese dioxide in dichloromethaneor benzene; or the Dess-Martin oxidation which is conducted using theDess-Martin periodinane in dichloromethane. Preferred oxidationreactions are the Dess-Martin oxidation, PDC oxidation or Swernoxidation in dichloromethane.

The reaction temperature depends on the starting material, solvent,oxidizing agent and the like and is usually between −78° C. and 100° C.,preferably between −78° C. and 30° C.

The reaction time depends on the starting material, solvent, oxidizingagent, reaction temperature and the like and is usually from 10 minutesto 2 days, preferably from 30 minutes to 24 hours.

Step J2

Step J2 is a process for the preparation of α,β-unsaturated esters ofphosphoric acid of formula (XXXV) and is accomplished by reaction of analdehyde compound of formula (XXXIII) with a compound of general formula(XXXIV) in the presence of a base in an inert solvent.

The inert solvent employed in the above reaction is not particularlyrestricted provided that it can dissolve the starting materials to someextent, and is preferably an aromatic hydrocarbon such as benzene,toluene, or xylene; a halogenated hydrocarbon such as dichloromethane,chloroform, or carbon tetrachloride; an ether such as diethyl ether,diisopropyl ether, tert-butyl methyl ether, or tetrahydrofuran; anitrile such as acetonitrile or isobutyronitrile; an amide such asformamide; or a sulfoxide such as dimethyl sulfoxide. The solvent ismore preferably an aromatic hydrocarbon or ether (most preferablybenzene or tetrahydrofuran).

The base employed in the above reaction is not particularly restrictedprovided that a carbanion corresponding to the compound of formula(XXXIV) can be produced by the base, and is preferably an alkali metalcarbonate such as sodium carbonate or potassium carbonate; an alkalimetal hydrogencarbonate such as sodium hydrogencarbonate or potassiumhydrogencarbonate; an alkali metal hydride such as sodium hydride orpotassium hydride; an alkali metal hydroxide such as sodium hydroxide orpotassium hydroxide; an alkali metal alkoxide such as sodium methoxide,sodium ethoxide, potassium methoxide or potassium ethoxide; an organicamine such as N-methylmorpholine or triethylamine; or an organometallicbase such as butyllithium or lithium diisopropylamide. The base is morepreferably an alkali metal alkoxide, an alkali metal hydride or anorganometallic base, and most preferably sodium hydride.

The reaction temperature depends on the starting material, solvent,phosphonium salt, base, and the like and is usually between −80° C. and100° C., preferably between −20° C. and 50° C.

The reaction time depends on the starting material, solvent, phosphoniumsalt, base, and the like and is usually from 10 minutes to 2 days,preferably from 10 minutes to 12 hours.

Step J3

Step J3 is a process for the preparation of compounds of general formula(III) and is accomplished by reduction of an unsaturated ester ofphosphoric acid of formula (XXXV) under an atmosphere of hydrogen in thepresence of a catalyst for catalytic hydrogenation in an inert solvent,followed by, if necessary, removal of the protecting group of the amino,hydroxyl, carboxyl and/or phosphoric acid groups.

The inert solvent employed in the reaction of the unsaturated ester ofphosphoric acid of formula (XXXV) is not particularly restrictedprovided that it has no adverse effect on the reaction and can dissolvethe starting materials to some extent, and is preferably an alcohol suchas methanol, ethanol, or isopropanol, an ether such as diethyl ether,diisopropyl ether, tert-butyl methyl ether, tetrahydrofuran, or dioxane;an aromatic hydrocarbon such as benzene, toluene, or xylene; analiphatic hydrocarbon such as hexane or cyclohexane; or an ester such asethyl acetate or propyl acetate. The solvent is preferably an alcohol(most preferably methanol or ethanol).

The catalyst employed in the above catalytic hydrogenation is preferablypalladium-charcoal, palladium hydroxide-charcoal, palladium black,platinum oxide, platinum black, rhodium-aluminum oxide,triphenylphosphine-rhodium chloride (Wilkinson complex),palladium-barium sulfate or Raney nickel. The more preferred catalystsare palladium-charcoal and triphenylphosphine-rhodium chloride(Wilkinson complex).

The pressure of hydrogen is not particularly restricted and is from 1 to10 atmospheric pressures.

The reaction temperature depends on the starting material, solvent,base, and the like and is usually between 0° C. and 100° C. (preferablybetween 0° C. and 50° C.)

The reaction time depends on the starting material,reaction-temperature, solvent, and base and is usually from 5 minutes to48 hours (preferably from 30 minutes to 24 hours).

After the reaction, the desired compound of each reaction can beisolated from the reaction mixture by conventional treatments, forexample, if necessary, neutralization of the reaction mixture, ordecomposition of the oxidizing agent with a reducing agent if theoxidizing agent is present in the reaction mixture, or filtration of thereaction mixture when insoluble material is present in the reactionmixture, addition of a solvent immiscible with water such as ethylacetate to the neutralized solution or the filtrate, separation of theorganic layer containing the desired compound, washing the resultingorganic layer with water, drying of the organic layer over anhydrousmagnesium sulfate, anhydrous sodium sulfate, anhydrous sodiumhydrogencarbonate or the like, and then evaporation of the organicsolvent to give the desired product. The product thus obtained, ifnecessary, is further purified by conventional procedures in organicchemistry, for example by recrystallization, reprecipitation,chromatography or an appropriate combination of these isolation orpurification procedures.

If necessary, the removal of the protecting group of the amino group,the removal of the protecting group of the hydroxyl group, or theremoval of the protecting group of the carboxyl group can beaccomplished by the same procedures as those indicated in Step A7hereinbefore, and the removal of the protecting group of phosphoric acidcan be accomplished by the same procedure as that indicated in Step I1hereinbefore.

Amino alcohol derivatives of general formula (I), phosphate derivativesof general formula (II), phosphonic acid derivatives of general formula(III), pharmacologically acceptable salts thereof, or pharmacologicallyacceptable esters thereof of the present invention exhibit excellentimmunosuppressive activity with low toxicity. Therefore, pharmaceuticalcompositions comprising, as an active ingredient, compounds of formula(I), (II), or (III), pharmacologically acceptable salts thereof, orpharmacologically acceptable esters thereof of the present invention areuseful as preventive or therapeutic agents (particularly therapeuticagents) for warm-blooded animals (particularly humans) for autoimmunediseases or other immunology-related diseases such as rejection causedby transplantation of various organs or skin, systemic lupuserythematosus, rheumatoid arthritis, polymyositis, fibrositis, skeletalmuscle inflammation, arthrosteitis, osteoarthritis, dermatomyositis,scleoderma, Behcet's syndrome, Crohn's disease, ulcerative colitis,autoimmune hepatitis, aplastic anemia, idiopathic thrombocytopenicpurpura, autoimmune hemolytic anemia, multiple sclerosis, autoimmunebullosis, psoriasis vulgaris, vasculitis syndrome, Wegener's granuloma,uveitis, Sjogren's syndrome, idiopathic interstitial pneumonia,Goodpasture's syndrome, sarcoidosis, allergic granulomatous angitis,bronchial asthma, myocarditis, cardiomyopathy, aortitis syndrome, postmyocardial infarction syndrome, primary pulmonary hypertension, minimalchange neohrotic syndrome, membranous nephropathy, membranoproliferativeglomerulonephritis, focal glomerular sclerosis, crescenticglomerulonephritis, myasthenia gravis, inflammatory neuropathy, atopicdermatitis, chronic actinic dermatitis, photosensitivity, pressuresores, Sydenham's chorea, sclerosis, adult-onset type diabetes mellitus,insulin dependent diabetes mellitus, juvenile diabetes mellitus,atherosclerosis, glomerular nephritis, IgA nephropathy,tubulointerstitial nephritis, primary biliary cirrhosis, primarysclerosing cholangitis, fulminant hepatitis, viral hepatitis, GVHD,contact dermatitis, and sepsis; diseases of infection by fungus,mycoplasma, virus, and protozoan and the like; cardiovascular diseasessuch as cardiac failure, cardiac hypertrophy, arrhythmia, anginapectoris, cardiac ischemia, arterial embolism, aneurysm, varix, andcirculation disorders; brain diseases such as Alzheimer's disease,dementia, Parkinson's disease, stroke, brain infarction, brain ischemia,depression, manic-depressive illness, schizophrenia, Huntington'schorea, epilepsy, convulsion, attention deficit disorder, encephalitis,cerebral meningitis, loss of appetite, and hyperphagia; and variousdiseases such as lymphoma, leukemia, diuresis, pollakisuria, anddiabetic retinopathy (particularly, autoimmune diseases such asrejection caused by transplantation of various organs or skin, systemiclupus erythematosus, rhematoid arthritis, multiple sclerosis, and atopicdermatitis).

The compounds of general formula (I), (II), or (III), pharmacologicallyacceptable salts thereof, or pharmacologically acceptable esters thereofof the present invention can be administered for the treatment orprevention of the above-mentioned diseases in a suitable dosage form,which is prepared from the compound alone or by mixing with a suitablepharmacologically acceptable carrier, i.e., excipient and/or diluent,such as tablets, capsules, granules, powders or syrups for oraladministration, or injections or suppositories for parenteraladministration.

Preparations are prepared by conventionally known methods using additiveagents such as excipients (for instance, organic excipients includingsugar derivatives such as lactose, sucrose, glucose, mannitol, andsorbitol; starch derivatives such as corn starch, potato starch,α-starch, and dextrin; cellulose derivatives such as crystallinecellulose; gum arabic; dextran; pullulan; and inorganic excipientsincluding silicate derivatives such as light anhydrous silicic acid,synthetic aluminum silicate, calcium silicate, and magnesiumaluminometasilicate; phosphates such as calcium hydrogenphosphate;carbonates such as calcium carbonate; and sulfates such as calciumsulfate), lubricants (for instance, stearic acid, metal salts of stearicacid such as calcium stearate and magnesium stearate; talc; colloidalsilica; waxes such as veegum and spermaceti; boric acid; adipic acid;sulfates such as sodium sulfate; glycol; fumaric-acid; sodium benzoate;DL-leucine; sodium fatty acid; laurylsulfates such as sodium laurylsulfate and magnesium lauryl sulfate; silicates such as silicicanhydride and silicic hydrate; and the starch derivatives describedabove can be listed), binders (for instance, hydroxypropylcellulose,hydroxypropylmethylcellulose, polyvinylpyrrolidone, Macrogol, andsimilar excipients to those described above), disintegrants (forinstance, cellulose derivatives such as low-substitutedhydroxypropylcellulose, carboxymethylcellulose, calciumcarboxymethylcellulose, and internally crosslinked sodiumcarboxymethylcellulose; and chemically modified starch/cellulosederivatives such as carboxymethylstarch, sodium carboxymethylstarch, andcrosslinked polyvinylpyrrolidone), stabilizers (for instance, para-oxybenzoates such as methylparaben and propylparaben; alcohols such aschlorobutanol, benzylalcohol, and phenylethylalcohol; benzalkoniumchloride; phenols such as phenol and cresol; thimerosal; dehydroaceticacid; and sorbic acid), flavors (for instance, conventionally employedsweeteners, acidifiers, and flavors), diluents, and the like.

The dosage varies depending on the symptoms, age, etc. of the patient.For example, in the case of oral administration, it is desirable toadminister 0.05 mg (preferably 5 mg) as a lower limit and 200 mg(preferably 40 mg) as an upper limit per one time for a human adult andone to six times per day depending on the symptoms of the patient.

In the case of intravenous administration, it is desirable to administer0.01 mg (preferably 1 mg) as a lower limit and 100 mg (preferably 10 mg)as an upper limit per one time for a human adult and one to six timesper day depending on the symptoms of the patient.

The present invention will further be exemplified in more detail by theExamples, Reference examples, Formulation examples, and Test examples.However the scope of the present invention is not limited by theseExamples.

EXAMPLES Example 1 (2R)-2-Amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)furan-2-yl]butan-1-ol oxalate (Exemplification Compound Number: 1-621having Formula Ia-1) (1a)(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-[5-(5-phenylpent-1-ynyl)furan-2-yl]butane

To a suspension of(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(5-bromofuran-2-yl)butane(0.3016 g, 0.91 mmol) obtained in Reference example 6,5-phenylpent-1-yne (0.3974 g, 2.76 mmol),dichlorobis(triphenylphosphine)palladium(II) (63.0 mg, 0.090 mmol) andcopper(I) iodide (35.4 mg, 0.19 mmol) in N,N-dimethylformamide (9.0 ml)was added triethylamine (1.25 ml, 9.0 mmol) with stirring, and theresulting mixture was stirred at room temperature under a nitrogenatmosphere for 10 hours. After stirring, saturated aqueous ammoniumchloride solution was added to the reaction mixture to quench thereaction, and to the resulting mixture were furthermore added water andethyl acetate. The resulting mixture was stirred at room temperature for30 minutes and then extracted with ethyl acetate. The extract was washedsuccessively with water and saturated aqueous sodium chloride solutionand dried over anhydrous sodium sulfate. After filtration, the solventwas removed in vacuo, and the residue was purified by chromatography ona silica gel column using a mixed solvent of ethyl acetate and hexane(1:1) as the eluent to afford the title compound (0.2841 g, yield: 79%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 7.31–7.27 (m, 2H), 7.22–7.18 (m,3H), 6.38 (d, 1H, J=3.2 Hz), 5.98 (d, 1H, J=3.2 Hz), 5.36 (br s, 1H),4.29 (d, J=11.2 Hz), 4.18 (d, 1H, J=11.2 Hz), 2.77 (t, 2H, J=7.8 Hz),2.64 (dt, 2H, J=8.5 Hz, 17.0 Hz), 2.44 (t, 2H, J=7.1 Hz), 2.30–2.22 (m,1H), 2.09 (s, 3H), 2.01–1.88 (m, 6H), 1.35 (s; 3H).

IR spectrum ν_(max) cm⁻¹ (CHCl₃): 3691, 3444, 2947, 1737, 1681, 1601,1511, 1453, 1374, 1251, 1042, 812, 803.

Mass spectrum (FAB⁺) m/z: 396 ((M+H)⁺).

(1b)(2R)-2-Amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)furan-2-yl]butan-1-oloxalate

To a solution of(2R)-1-acetoxy-2-acetylamino-2-methyl-4-[5-(5-phenylpent-1-ynyl)furan-2-yl]butane(0.2710 g, 0.69 mmol) obtained in Example (1a) in a mixed solvent oftetrahydrofuran (1.4 ml) and methanol (1.4 ml) were added successivelywater (1.4 ml) and lithium hydroxide monohydrate (0.2854 g, 6.80 mmol)with stirring, and the resulting mixture was stirred at 50° C. for 4hours. After cooling, water was added to the reaction mixture, and theresulting mixture was extracted with dichloromethane. The extract waswashed with saturated aqueous sodium chloride solution and dried overanhydrous sodium sulfate. After filtration, the solvent was removed invacuo, and the residue was purified by chromatography on a basic silicagel column (NH type) using a mixed solvent of dichloromethane andmethanol (100:1) as the eluent to afford the crude(2R)-2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)furan-2-yl]butan-1-ol(0.2072 g).

Subsequently, to a solution of the crude product thus obtained inmethanol was added anhydrous oxalic acid (98% pure) (59.2 mg, 0.64mmol), and the resulting mixture was stirred at room temperature for 30minutes. After stirring, the reaction mixture was evaporated in vacuo,and ethyl acetate was added to the residue. The crystals precipitatedwere collected by filtration, washed with ethyl acetate and dried invacuo to afford the title compound (0.2344 g, yield: 91 %).

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 7.29–7.25 (m, 2H), 7.21–7.14 (m,3H), 6.40 (d, 1H, J=3.0 Hz), 6.09 (d, 1H, J=3.0 Hz), 3.59 (d, 1H, J=11.6Hz), 3.50 (d, 1H, J=11.6 Hz), 2.77–2.65 (m, 4H), 2.41 (t, 2H, J=7.0 Hz),2.07–1.83 (m, 4H), 1.29 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3353, 3128, 2940, 1720, 1645, 1614,1598, 1542, 1403, 1220, 1078, 789, 713, 700.

Mass spectrum (FAB⁺) m/z: 312((M+H)⁺; as free form of title compound).

Example 2(2R)-2-Amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]butan-1-oloxalate (Exemplification Compound Number: 1-570 having Formula Ia-1)

The title compound was synthesized in a yield of 68% using(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(5-bromofuran-2-yl) butaneobtained in Reference example 6 and 5-cyclohexylpent-1-yne as thestarting materials by conducting successively the reactions similar tothose mentioned in Examples (1a) and (1b).

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 6.36 (d, 1H, J=3.1 Hz), 6.08 (d, 1H,J=3.1 Hz), 3.59 (d, 1H, J=11.5 Hz), 3.49 (d, 1H, J=11.5 Hz), 2.77–2.64(m, 2H), 2.39 (t, 2H, J=7.2 Hz), 2.07–1.90 (m, 2H), 1.76–1.54 (m, 7H),1.35–1.12 (m, 9H), 0.96–0.86 (m, 2H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3362, 3124, 2923, 2850, 1720, 1611,1597, 1542, 1467, 1403, 1279, 1220, 1067, 967, 791, 721, 700.

Mass spectrum (FAB⁺) m/z: 318((M+H)⁺; as free form of title compound).

Example 3(2R)-2-Amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]butan-1-oloxalate (Exemplification Compound Number: 1-842 having Formula Ia-1)

The title compound was synthesized in a yield of 66% using(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(5-iodofuran-2-yl) butaneobtained in Reference example 7 and 4-cyclohexyloxybut-1-yne as thestarting materials by conducting successively the reactions similar tothose mentioned in Examples (1a) and (1b).

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 6.40 (d, 1H, J=3.3 Hz), 6.09 (d, 1H,J=3.3 Hz), 3.63 (t, 2H, J=6.6 Hz), 3.58 (d, 1H, J=11.7 Hz), 3.50 (d, 1H,J=11.7 Hz), 3.39–3.32 (m, 1H), 2.77–2.62 (m, 4H), 2.07–1.89 (m, 4H),1.77–1.73 (m, 2H), 1.56–1.53 (m, 1H), 1.36–1.23 (m, 8H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3360, 3099, 2932, 2857, 1719, 1614,1597, 1542, 1403, 1219, 1106, 967, 785, 720, 711.

Mass spectrum (FAB⁺) m/z: 320((M+H)⁺; as free form of title compound).

Example 4(2R)-2-Amino-2-methyl-4-{5-[3-(3,4-dimethylphenyloxy)prop-1-ynyl]furan-2-yl}butan-1-oloxalate (Exemplification Compound Number: 1-1836 Having Formula Ia-1)

The title compound was synthesized in a yield of 46% using(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(5-bromofuran-2-yl) butaneobtained in Reference example 6 and 3-(3,4-dimethyl) phenyloxy-1-propyneas the starting materials by conducting successively the reactionssimilar to those mentioned in Examples (1a) and (1b).

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 7.02 (d, 1H, J=8.3 Hz), 6.77 (d, 1H,J=2.7 Hz), 6.71 (dd, 1H, J=8.3 Hz, 2.7 Hz), 6.55 (d, 1H, J=3.2 Hz), 6.14(d, 1H, J=3.2 Hz), 4.88 (s, 2H), 3.58 (d, 1H, J=11.7 Hz), 3.49 (d, 1H,J=11.7 Hz), 2.79–2.66 (m, 2H), 2.23 (s, 3H), 2.19 (s, 3H),2.07–1.90 (m,2H), 1.28 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3358, 3134, 2921, 2582, 1720, 1649,1616, 1579, 1542, 1499, 1370, 1286, 1250, 1223, 1166, 1122, 1046, 1025,802, 712.

Mass spectrum (FAB⁺) m/z: 328((M+H)⁺; as free form of title compound).

Example 5(2R)-2-Amino-2-methyl-4-[5-(5-phenylpentanoyl)furan-2-yl]butan-1-oloxalate (Exemplification Compound Number: 1-1093 having Formula Ia-1)

To a solution of(2R)-2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)furan-2-yl]butan-1-ol(0.3440 g, 1.11 mmol) obtained in Example (1b) in methanol (3.5 ml) wasadded a 6N aqueous sulfuric acid solution (3.5 ml) with stirring, andthe resulting mixture was refluxed for 4 hours. After cooling, thereaction mixture was neutralized with saturated aqueous sodiumhydrogencarbonate solution, and then water and dichloromethane werefurthermore added. The resulting mixture was stirred for 30 minutes andextracted with dichloromethane. The extract was washed with saturatedaqueous sodium chloride solution and dried over anhydrous sodiumsulfate. After filtration, the solvent was removed in vacuo, and theresidue was purified by chromatography on a basic silica gel column (NHtype) using a mixed solvent of dichloromethane and methanol (100:1) asthe eluent to afford the reaction product.

Subsequently, to a solution of the reaction product thus obtained inmethanol was added anhydrous oxalic acid (98% pure) (91.8 mg, 1.00mmol), and the resulting mixture was stirred at room temperature for 30minutes. After stirring, the reaction mixture was evaporated in vacuo,and ethyl acetate was added to the residue. The crystals precipitatedwere collected by filtration, washed with ethyl acetate and dried invacuo to afford the title compound (0.3687 g, yield: 90%).

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 7.31 (d, 1H, J=3.6 Hz), 7.25–7.22(m, 2H), 7.17–7.12 (m, 3H), 6.36 (d, 1H, J=3.6 Hz), 3.61 (d, 1H, J=11.6Hz), 3.52 (d, 1H, J=11.6 Hz), 2.89–2.76 (m, 4H), 2.64 (t, 2H, J=7.2 Hz),2.13–1.95 (m, 2H), 1.75–1.63 (m, 4H), 1.30 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3108, 3027, 2981, 2935, 1718, 1698,1661, 1604, 1542, 1516, 1202, 1093, 1082, 1047, 797, 700.

Mass spectrum (FAB⁺) m/z: 330((M+H)⁺; as free form of title compound).

Example 6(2R)-2-Amino-2-methyl-4-[5-(5-phenylpentyl)furan-2-yl]butan-1-ol oxalate(Exemplification Compound Number: 1-93 having formula Ia-1) (6a)(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-[5-(5phenylpentyl)furan-2-yl]butane

To a suspension of 10% palladium-charcoal (50% wet with water) (25 mg)in methanol (1 ml) was added a solution of(2R)-1-acetoxy-2-acetylamino-2-methyl-4-[5-(5-phenylpent-1-ynyl)furan-2-yl]butane (0.1245 g, 0.32 mmol) obtained in Example (1a) inmethanol (1.5 ml), and the resulting mixture was stirred at roomtemperature under a hydrogen atmosphere for 8 hours. After stirring, theinternal atmosphere was replaced with nitrogen, and thepalladium-charcoal in the reaction mixture was filtered off usingcelite, which was washed with ethyl acetate. The filtrate and thewashings were combined and evaporated to dryness in vacuo. The residueobtained was purified by chromatography on a silica gel column using amixed solvent of ethyl acetate and hexane (3:2) as the eluent to affordthe title compound (0.1029 g, yield: 82%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 7.29–7.26 (m, 2H), 7.19–7.16 (m,3H), 5.87 (d, 1H, J=3.0 Hz), 5.83 (d, 1H, J=3.0 Hz), 5.36 (br s, 1H),4.31 (d, 1H, J=11.2 Hz), 4.17 (d, 1H, J=11.2 Hz), 2.64–2.54 (m, 4H),2.25–2.17 (m, 1H, 2.08 (s, 3H), 2.05–1.91 (m, 1H), 1.92 (s, 3H),1.69–1.60 (m, 4H), 1.43–1.37 (m, 2H), 1.35 (s, 3H).

Mass spectrum (FAB⁺) m/z: 400((M+H)⁺; as free form of title compound).

(6b) (2R)-2-Amino-2-methyl-4-[5-(5-phenylpentyl)furan-2-yl]butan-1-oloxalate

To a solution of(2R)-1-acetoxy-2-acetylamino-2-methyl-4-[5-(5-phenylpentyl)furan-2-yl]butane(99.7 mg, 0.25 mmol) obtained in Example (6a) in a mixed solvent oftetrahydrofuran (0.5 ml) and methanol (0.5 ml) were added successivelywater (0.5 ml) and lithium hydroxide monohydrate (0.1037 g, 2.47 mmol),and the resulting mixture was stirred at 50° C. for 4 hours. Aftercooling, water was added to the reaction mixture, and the resultingmixture was extracted with dichloromethane. The extract was washed withsaturated aqueous sodium chloride solution and dried over anhydroussodium sulfate. After filtration, the solvent was removed in vacuo, andthe residue was purified by chromatography on a basic silica gel column(NH type) using a mixed solvent of dichloromethane and methanol (100:1)as the eluent to afford(2R)-2-amino-2-methyl-4-[5-(5-phenylpentyl)furan-2-yl]butan-1-ol (74.6mg, yield: 95%)

Subsequently, to a solution of the reaction product thus obtained inmethanol (2.3 ml) was added anhydrous oxalic acid (98% pure) (21.1 mg,0.23 mmol) with stirring, and the resulting mixture was stirred at roomtemperature for 1 hour. After stirring, the reaction mixture wasevaporated in vacuo, and ethyl acetate was added to the residue. Thecrystals precipitated were collected by filtration, washed with ethylacetate and dried in vacuo to afford the title compound (78.1 mg, yield:85%)

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 7.25–7.21 (m, 2H), 7.15–7.11 (m,3H), 5.94 (d, 1H, J=3.2 Hz), 5.87 (d, 1H, J=3.2 Hz), 3.58 (d, 1H, J=11.6Hz), 3.49 (d, 1H, J=11.6 Hz), 2.69–2.53 (m, 6H), 2.04–1.88 (m, 2H),1.67–1.59 (m, 4H), 1.40–1.32 (m, 2H), 1.28 (s,3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3119, 3025, 2979, 2928, 2855, 1719,1610, 1543, 1466, 1402, 1197, 1094, 1078, 1012, 786, 746, 721, 699.

Mass spectrum (FAB⁺) m/z: 316((M+H)⁺; as free form of title compound).

Example 7(2R)-2-Amino-2-methyl-4-[5-(4-cyclohexylmethoxyphenyl)furan-2-yl]butan-1-oloxalate (Exemplification Compound Number: 1-1433 having Formula Ia-1)(7a)(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-[5-(4-cyclohexylmethoxyphenyl)furan-2-yl]butane

(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-(5-iodofuran-2-yl)butane (0.2047g, 0.51 mmol) obtained in Reference example 7,2-(4-cyclohexylmethoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane(0.2400 g, 0.7.6 mmol), dichlorobis(triphenylphosphine)palladium(II)(36.1 mg, 0.051 mmol) and cesium carbonate (0.6738 g, 2.03 mmol) weresuspended in a mixed solvent of dimethoxyethane (4.0 ml) and water (1ml) and stirred at 80° C. for 4 hours. After cooling, water was added tothe reaction mixture, and the resulting mixture was extracted withdichloromethane. The extract was washed with saturated aqueous sodiumchloride solution and dried over anhydrous sodium sulfate. Afterfiltration, the solvent was removed in vacuo.

Subsequently, to a solution of the residue obtained in dichloromethane(5.0 ml) were added successively triethylamine (0.72 ml, 5.2 mmol),acetic anhydride (0.24 ml, 2.6 mmol) and 4-dimethylaminopyridine (6.4mg, 0.052 mmol), and the resulting mixture was stirred at roomtemperature for 2 hours. After stirring, methanol (0.10 ml, 2.5 mmol)was added to quench the reaction, and to the reaction mixture werefurthermore added ethyl acetate and water, and then the resultingmixture was extracted with ethyl acetate. The extract was washedsuccessively with water, saturated aqueous sodium hydrogencarbonatesolution and saturated aqueous sodium chloride solution, and dried overanhydrous sodium sulfate. After filtration, the solvent, was removed invacuo, and the residue was purified by chromatography on a silica gelcolumn using a mixed solvent of ethyl acetate and hexane (3:2) as theeluent to afford the title compound (45.3 mg, yield: 20%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 7.55–7.51 (m, 2H), 7.00–6.87 (m,2H), 6.39 (d, 1H, J=3.1 Hz), 6.06 (d, 1H, J=3.1 Hz), 5.36 (br s, 1H),4.34 (d, J=11.2 Hz), 4.20 (d, 1H, J=11.2 Hz), 3.76 (d, 2H, J=2.5 Hz),2.73–2.69 (m, 2H), 2.35–2.27 (m, 1H), 2.09 (s, 3H), 2.08–1.99 (m, 1H),1.91 (s, 3H), 1.93–1.69 (m, 6H), 1.38 (s, 3H), 1.37–1.18(m, 3H),1.10–1.00(m, 2H).

Mass spectrum (FAB⁺) m/z: 442((M+H)⁺), 441(M⁺).

(7b) (2R)-2-Amino-2-methyl-4-[5-(4-cyclohexylmethoxyphenyl)furan-2-yl]butan-1-ol oxalate

To a solution of(2R)-1-acetoxy-2-acetylamino-2-methyl-4-[5-(4-cyclohexylmethoxyphenyl)furan-2-yl]butane(44.0 mg, 0.10 mmol) obtained in Example (7a) in a mixed solvent oftetrahydrofuran (0.4 ml) and methanol (0.4 ml) were added successivelywater (0.4 ml) and lithium hydroxidemonohydrate (43.6 mg, 1.04 mmol),and the resulting mixture was stirred at 50° C. for 4 hours. Aftercooling, water was added to the reaction mixture, and the resultingmixture was extracted with dichloromethane. The extract was washed withsaturated aqueous sodium chloride solution and dried over anhydroussodium sulfate. After filtration, the solvent was removed in vacuo, andthe residue was purified by chromatography on a basic silica gel column(NH type) using a mixed solvent of dichloromethane and methanol (50:1)as the eluent to afford the reaction product (35.2 mg, yield: 99%).

Subsequently, to a solution of the reaction product thus obtained inmethanol (2.0 ml) was added anhydrous oxalic acid (98% pure) (8.9 mg,0.10 mmol), and the resulting mixture was stirred at room temperaturefor 30 minutes. After stirring, the reaction mixture was evaporated invacuo, and acetone was added to the residue. The crystals precipitatedwere collected by filtration, washed with acetone and dried in vacuo toafford the title compound (28.2 mg, yield: 66%).

¹H-NMR spectrum (CD₃OD-DMSO-d₆, 400 MHz) δ: 7.55 (d, 2H, J=8.7 Hz), 6.93(d, 2H, J=8.7 Hz), 7.16 (t, 1H, J=2.0 Hz), 6.53 (d, 1H, J=3.2 Hz), 6.17(d, 1H, J=3.2 Hz), 3.79 (d, 2H, J=6.4 Hz), 3.58 (d, 1H, J=11.7 Hz), 3.50(d, 1H, J=11.7 Hz), 3.28–3.27 (m, 2H), 2.09–1.69 (m, 8H), 1.38–1.04 (m,8H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3387, 3235, 2924, 2852, 2578, 1618,1568, 1499, 1466, 1448, 1390, 1288, 1245, 1174, 1024, 828, 783, 765.

Mass spectrum (FAB⁺) m/z: 358((M+H)⁺).

Example 8(2R)-2-Amino-2-methyl-4-{5-[3-(2-cyclohexylethoxy)phenyl]furan-2-yl}butan-1-oloxalate (Exemplification Compound Number: 1-1444 having Formula Ia-1)

The title compound was synthesized in a yield of 21% using(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(5-iodofuran-2-yl) butaneobtained in Reference example 7 and 2-[3-(2-cyclohexylethoxy)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane as the startingmaterials by conducting the reaction similar to that mentioned inExample 7.

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 7.27 (t, 1H, J=8.0 Hz), 7.21 (dd,1H, J=8.0 Hz, 2.0 Hz), 7.16. (t, 1H, J=2.0 Hz), 6.80 (dd, 1H, J=8.0 Hz,2.0 Hz), 6.69 (d, 1H, J=3.5 Hz), 6.21 (d, 1H, J=3.5 Hz), 4.04 (t, 2H,J=6.6 Hz), 3.61 (d, 1H, J=11.6 Hz), 3.52 (d, 1H, J=11.6 Hz), 2.83–2.78(m, 2H), 2.62–2.60 (m, 1H), 2.13–1.97 (m, 2H), 1.81–1.65. (m, 6H),1.59–1.49 (m, 1H.), 1.31–1.02 (m, 6H), 1.00–0.96 (m, 2H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3213, 2925, 2850, 2571, 1720, 1701,1614, 1600, 1578, 1563, 1548, 1449, 1300, 1216, 1205, 1052, 1033, 1017,863, 772, 721, 689.

Mass spectrum (FAB⁺) m/z: 372((M+H)⁺; as free form of title compound).

Example 9(2R)-2-Amino-2-methyl-4-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]butan-1-oloxalate (Exemplification compound Number: 1-621 having Formula Ia-2)

The title compound was synthesized in a yield of 57% using(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(1-methyl-5-iodopyrrol-2-yl)butaneobtained in Reference example 13 and 5-phenylpent-1-yne as the startingmaterials by conducting successively the reactions similar to thosementioned in Examples (1a) and (1b).

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 7.28–7.14 (m, 5H), 6.16 (d, 1H,J=3.7 Hz), 5.80 (d, 1H, J=3.7 Hz), 3.63 (d, 1H, J=11.6 Hz), 3.57 (s,3H), 3.54 (d, 1H, J=11.6 Hz), 2.77 (t, 2H, J=7.6 Hz), 2.66–2.61 (m, 2H),2.43 (t, 2H, J=7.0 Hz), 2.04–1.96 (m, 1H), 1.92–1.84 (m, 3H), 1.33(s,3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3212, 3026, 2935, 2897, 2571, 1719,1700, 1611, 1521, 1496, 1454, 1405, 1279, 1218, 1053, 767, 721, 700.

Mass spectrum (FAB⁺) m/z: 325((M+H)⁺; as free form of title compound).

Example 10(2R)-2-Amino-2-methyl-4-[1-methyl-5-(4-cyclohexyloxybut-1-ynyl)pyrrol-2-yl]butan-1-ol½-oxalate (Exemplification compound number: 1-842 having formula Ia-2)

The title compound was synthesized in a yield of 32% using(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(1-methyl-5-iodopyrrol-2-yl)butaneobtained in Reference example 13and 4-cyclohexyloxybut-1-yne as thestarting materials by conducting successively the reactions similar tothose mentioned in Examples (1a) and (1b).

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 6.13 (d, 1H, J=3.7 Hz), 5.79 (d, 1H,J=3.7 Hz), 3.65 (t, 2H, J=6.8 Hz), 3.61 (d, 1H, J=11.5 Hz), 3.56 (s,3H), 3.53 (d, 1H, J=11.5 Hz), 3.39–3.34 (m, 1H), 2.68–2.61 (m, 4H),2.01–1.83 (m, 4H), 1.78–1.74 (m, 2H), 1.56–1.54 (m, 1H), 1.35–1.21 (m,8H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3348, 2931, 2856, 1590, 1452, 1364,1309, 1106, 762.

Mass spectrum (FAB⁺) m/z: 333 ((M+H)⁺; as free form of title compound).

Example 11(2R)-2-Amino-2-methyl-4-{1-methyl-5-[3-(4-methylphenyloxy)prop-1-ynyl]pyrrol-2-yl}butan-1-ol½-oxalate (Exemplification compound number: 1-833 having formula Ia-2)

The title compound was synthesized in a yield of 29% using(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(1-methyl-5-iodopyrrol-2-yl)butaneobtained in Reference example 13 and 3-(4-methylphenyloxy)-1-propyne asthe starting materials by conducting successively the reactions similarto those mentioned in Examples (1a) and (1b).

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 7.09 (d, 1H, J=8.5 Hz), 6.90 (d, 1H,J=8.5 Hz), 6.26 (d, 1H, J=3.7 Hz), 5.83 (d, 1H, J=3.7 Hz), 4.93 (s, 2H),3.60 (d, 1H, J=11.6 Hz), 3.53 (d, 1H, J=11.6 Hz), 3.51 (s, 3H),2.65–2.60 (m, 2H), 2.26 (s, 3H), 2.01–1.93 (m, 1H), 1.89–1.82 (m, 1H),1.30 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3356, 2944, 2602, 2220, 1586, 1510,1455, 1365, 1295, 1228, 1178, 1071, 1042, 1015, 815, 762.

Mass spectrum (FAB⁺) m/z: 327 ((M+H)⁺; as free form of title compound).

Example 12(2R)-2-Amino-2-methyl-4-{1-methyl-5-[3-(3,4-dimethylphenyloxy)prop-1-ynyl]pyrrol-2-yl}butan-1-ol½-oxalate (Exemplification compound number: 1-1836 having formula Ia-2)

The title compound was synthesized in a yield of 33% using(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(1-methyl-5-iodopyrrol-2-yl)butaneobtained in Reference example 13 and 3-(3,4-dimethylphenyloxy)-1-propyneas the starting materials by conducting successively the reactionssimilar to those mentioned in Examples (1a) and (1b).

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 7.02 (d, 1H, J=8.2 Hz), 6.81 (d, 1H,J=2.5 Hz), 6.73 (dd, 1H, J=8.2 Hz, 2.5 Hz), 6.26 (d, 1H, J=3.9 Hz), 5.83(d, 1H, J=3.9 Hz), 4.91 (s, 2H), 3.61 (d, 1H, J=11.4 Hz), 3.53 (d, 1H,J=11.4 Hz), 3.52 (s, 3H), 2.65–2.61 (m, 2H), 2.23 (s, 3H), 2.18 (s, 3H),1.99–1.93 (m, 1H), 1.90–1.82 (m, 1H), 1.31 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3420, 2943, 2631, 2213, 1584, 1503,1455, 1365, 1301, 1251, 1207, 1163, 1025, 806, 762.

Mass spectrum (FAB⁺) m/z: 341 ((M+H)⁺; as free form of title compound).

Example 13(2R)-2-Amino-2-methyl-4-[5-(4-phenylbut-1-ynyl)furan-2-yl]butan-1-oloxalate (Exemplification compound number: 1-559 having formula Ia-1)

The title compound was synthesized in a yield of 61% using(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(5-bromofuran-2-yl)butaneobtained-in Reference example 6 and 4-phenylbut-1-yne as the startingmaterials by conducting successively the reactions similar to thosementioned in Examples (1a) and (1b).

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 7.29–7.17 (m, 5H), 6.35 (d, 1H,J=3.4 Hz), 6.07 (d, 1H, J=3.4 Hz), 3.59 (d, 1H, J=11.7 Hz), 3.50 (d, 1H,J=11.7 Hz), 2.87 (t, 2H, J=7.3 Hz), 2.77–2.64 (m, 4H), 2.06–1.89 (m,2H), 1.29 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3353, 3140, 2924, 2896, 1724, 1651,1617, 1598, 1542, 1403, 1221, 1075, 1054, 1010, 784, 713, 501.

Mass spectrum (ESI⁺) m/z: 298 ((M+H)⁺; as free form of title compound).

Example 14(2R)-2-Amino-2-methyl-4-{5-[5-(4-chlorophenyl)pent-1-ynyl]furan-2-yl}butan-1-oloxalate (Exemplification compound number: 1-628 having formula Ia-1)

The title compound was synthesized in a yield of 60% using(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(5-iodofuran-2-yl)butaneobtained in Reference example 7 and 5-(4-chlorophenyl)pent-1-yne as thestarting materials by conducting successively the reactions similar tothose mentioned in Examples (1a) and (1b).

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 7.28–7.25 (m, 2H), 7.20 (d, 1H,J=8.3 Hz), 6.40 (d, 1H, J=3.4 Hz), 6.09 (d, 1H, J=3.4 Hz), 3.59 (d, 1H,J=11.7 Hz), 3.51 (d, 1H, J,=11.7 Hz), 2.78–2.65 (m, 4H), 2.42 (t, 2H,J=6.8 Hz), 2.08–1.83 (m, 4H), 1.29 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr) 3257, 3105, 2936, 1718, 1598, 1540, 1493,1405, 1280, 1202, 1093, 1015, 828, 792, 721, 701, 502.

Mass spectrum (FAB⁺) m/z: 346 ((M+H)⁺; as free form of title compound).

Example 15(2R)-2-Amino-2-methyl-4-{5-[5-(3-trifluoromethylphenyl)pent-1-ynyl]furan-2-yl}butan-1-oloxalate (Exemplification compound number: 1-640 having formula Ia-1)

The title compound was synthesized in a yield of 58% using(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(5-iodofuran-2-yl)butaneobtained in Reference example 7 and5-(3-trifluoromethylphenyl)pent-1-yne as the starting materials byconducting successively the reactions similar to those mentioned inExamples (1a) and (1b).

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 7.51–7.48 (m, 4H), 6.41 (d, 1H,J=3.3 Hz), 6.10 (d, 1H, J=3.3 Hz), 3.59 (d, 1H, J=11.6 Hz), 3.51 (d, 1H,J=11.6 Hz), 2.85 (t, 2H, J=7.4 Hz), 2.78–2.66 (m, 2H), 2.44 (t, 2H,J=7.0 Hz), 2.08–1.87 (m, 4H), 1.29 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3358, 3139, 2935, 1722, 1651, 1615,1597, 1542, 1403, 1326, 1222, 1168, 1119, 1073, 797, 721, 713, 703, 503.

Mass spectrum (FAB⁺) m/z: 380 ((M+H)⁺; as free form of title compound).

Example 16(2R)-2-Amino-2-methyl-4-{5-[3-(4-methylphenyloxy)prop-1-ynyl]furan-2-yl}butan-1-oloxalate (Exemplification compound number: 1-833 having formula Ia-1)

The title compound was synthesized in a yield of 11% using(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(5-bromofuran-2-yl)butaneobtained in Reference example 6 and 3-(4-methylphenyloxy)-1-propyne asthe starting materials by conducting successively the reactions similarto those mentioned in Examples (1a) and (1b).

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 7.13–7.06 (m, 2H), 6.92–6.84 (m.2H), 6.55 (d, 1H, J=3.4 Hz), 6.13 (d, 1H, J=3.4 Hz), 4.90 (s, 2H), 3.59(d, 1H, J=11.7 Hz), 3.50 (d, 1H, J=11.7 Hz), 3.34–3.28 (m, 2H),2.80–2.64 (m, 2H), 2.27 (s, 3H), 2.07–1.87 (m, 2H), 1.28 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3352, 3138, 2921, 2893, 1727, 1653,1616, 1596, 1544, 1511, 1373, 1224, 1018, 713.

Mass spectrum (FAB⁺) m/z: 314 ((M+H)⁺; as free form of title compound).

Example 17(2R)-2-Amino-2-methyl-4-{5-[3-(4-methylthiophenyloxy)prop-1-ynyl]furan-2-yl}butan-1-oloxalate (Exemplification compound number: 1-838 having formula Ia-1)

The title compound was synthesized in a yield of 15% using(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(5-bromofuran-2-yl)butaneobtained in Reference example 6 and 3-(4-methylthiophenyloxy)-1-propyneas the starting materials by conducting successively the reactionssimilar to those mentioned in Examples (1a) and (1b).

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 7.30–7.25 (m, 2H), 6.99–6.94 (m,2H), 6.57 (d, 1H, J=3.5 Hz), 6.14 (d, 1H, J=3.5 Hz), 4.94 (s, 2H), 3.59(d, 1H, J=11.6 Hz), 3.50 (d, 1H, J=11.6 Hz), 2.80–2.65 (m, 2H), 2.42 (s,3H), 2.08–1.88 (m, 2H),

1.28 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3359, 3136, 3089, 2920, 2230, 1722,1646, 1618, 1594, 1542, 1493, 1373, 1279, 1230, 1073, 1039, 1015, 820,797, 712.

Mass spectrum (FAB⁺) m/z 346 ((M+H)⁺; as free form of title compound).

Example 18(2R)-2-Amino-2-methyl-4-[5-(4-phenyloxybut-1-ynyl)furan-2-yl]butan-1-oloxalate (Exemplification compound number: 1-893 having formula Ia-1)

The title compound was synthesized in a yield of 42% using(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(5-iodofuran-2-yl)butaneobtained in Reference example 7 and 4-phenyloxybut-1-yne as the startingmaterials by conducting successively the reactions similar to thosementioned in Examples (1a) and (1b).

¹H-NMR spectrum (DMSO-d₆, 400 MHz) δ: 7.32–7.28 (m, 2H), 6.98–6.93 (m,3H), 6.78 (d, 1H, J=3.2 Hz), 6.16 (d, 1H, J=3.2 Hz), 4.13 (t, 2H, J=6.4Hz), 3.40 (dd, 2H, J=19.8 Hz, 11.4 Hz), 2.93 (t, 2H, J=6.4 Hz), 2.66 (t,2H, J=8.5 Hz), 1.95–1.75 (m, 2H), 1.16 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3115, 2978, 2940, 1719, 1600, 1547,1498, 1248, 1204, 1081, 1039, 752, 700.

Mass spectrum (FAB⁺) m/z: 314 ((M+H)⁺; as free form of title compound),

Elemental analysis (% as C₁₉H₂₃NO₃.C₂H₂O₄)

Calculated: C, 62.52; H, 6.25; N, 3.47. Found: C, 62.47; H, 6.14; N,3.42.

Example 19(2R)-2-Amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]butan-1-olhydrochloride (Exemplification compound number: 1-570 having formulaIa-1) (19a)(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]butane

To a suspension of(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(5-iodofuran-2-yl)butane (4.1685g, 10.99 mmol) obtained in Reference example 7, 5-cyclohexylpent-1-yne(4.48 g, 29.8 mmol), dichlorobis(triphenylphosphine)palladium(II)(0.7730 g, 1.10 mmol) and copper(I) iodide (0.4205 g, 2.21 mmol) inN,N-dimethylformamide (110 ml) was added triethylamine (15.3 ml, 110.1mmol) with stirring, and the resulting mixture was stirred at 60° C.under a nitrogen atmosphere for 2 hours. After cooling, saturatedaqueous ammonium chloride solution was added to the reaction mixture toquench the reaction, and furthermore water and ethyl acetate were added.The resulting mixture was stirred at room temperature for 30 minutes andthen extracted with ethyl acetate. The extract was washed successivelywith water and saturated aqueous sodium chloride solution and dried overanhydrous sodium sulfate. After filtration, the solvent was removed invacuo, and the residue was purified by chromatography on a silica gelcolumn using a mixed solvent of ethyl acetate and hexane (3:2) as theeluent to afford the title compound (2.6576 g, yield: 60%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 6.36 (d, 1H, J=2.9 Hz), 5.97 (d, 1H,J=2.9 Hz), 5.36 (br s, 1H), 4.29 (d, J=11.0 Hz), 4.17 (d, 1H, J=11.0Hz), 2.63 (t, 2H, J=8.1 Hz), 2.40 (t, 2H, J=7.3 Hz), 2.29–2.21 (m, 1H),2.09 (s, 3H), 2.00–1.93 (m, 1H), 1.92 (s, 3H), 1.72–1.51 (m, 7H), 1.35(s, 3H), 1.33–1.08 (m, 6H), 0.93–0.84 (m, 2H).

Mass spectrum (FAB⁺) m/z: 402 ((M+H)⁺).

(19b)(2R)-2-Amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]butan-1-olhydrochloride

To a solution of(2R)-1-acetoxy-2-acetylamino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]butane(1.2996 g, 3.24 mmol) obtained in Example (19a) in a mixed solvent oftetrahydrofuran (6.4 ml) and methanol (6.4 ml) were added successivelywater (6.4 ml) and lithium hydroxide monohydrate (1.3590 g, 32.39 mmol)with stirring, and the resulting mixture was stirred at 50° C. for 4hours. After cooling, water was added to the reaction mixture, and theresulting mixture was extracted with dichloromethane. The extract waswashed with saturated aqueous sodium chloride solution and dried overanhydrous sodium sulfate. After filtration, the solvent was removed invacuo, and the residue was purified by chromatography on a basic silicagel column (NH type) using a mixed solvent of dichloromethane andmethanol (100:1) as the eluent to afford the crude(2R)-2-amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]butan-1-ol(1.0048 g).

Subsequently, to a solution of the crude product obtained above inmethanol (16 ml) was added a 4N hydrochloric acid-dioxane solution (0.79ml, 3.16 mmol) with stirring, and the resulting mixture was stirred atroom temperature for 10 minutes. After stirring, the reaction mixturewas evaporated in vacuo, and ether was added to the residue. Thecrystals precipitated were collected by-filtration, washed with etherand dried in vacuo to afford the title compound (1.0392 g, yield: 91%)

Melting point: 117–118° C.,

Angle of rotation: [α]_(D)=+2.43 (c=1.00, MeOH),

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 6.36 (d, 1H, J=3.3 Hz), 6.08 (d, 1H,J=3.3 Hz), 3.59 (d, 1H, J=11.6 Hz), 3.49 (d, 1H, J=11.6 Hz), 2.77–2.64(m, 2H), 2.39 (t, 2H, J=7.1 Hz), 2.07–1.89 (m, 2H), 1.76–1.54 (m, 7H),1.35–1.12 (m, 9H), 0.96–0.86 (m, 2H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3138, 2921, 2850, 2693, 2571, 1615,1595, 1534, 1448, 1402, 1369, 1298, 1197, 1058, 788.

Mass spectrum (FAB⁺) m/z: 318 ((M+H)⁺; as free form of title compound).

Example 20(2R)-2-Amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]butan-1-olhydrochloride (Exemplification compound number: 1-842 having formulaIa-1)

The title compound was synthesized in-a yield of 57% using(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(5-iodofuran-2-yl)butaneobtained in Reference example 7 and 4-cyclohexyloxybut-1-yne as thestarting materials by conducting successively the reactions similar tothose mentioned in Examples (19a) and (19b).

Melting point: 115–118° C.,

Angle of rotation: [α]_(D)=+2.63 (c=1.00, MeOH),

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 6.40 (d, 1H, J=3.4 Hz), 6.09 (d, 1H,J=3.4 Hz), 3.63 (t, 2H, J=6.6 Hz), 3.58 (d, 1H, J=11.6 Hz), 3.50 (d, 1H,J=11.6 Hz), 3.39–3.32 (m, 1H), 2.76–2.62 (m, 4H), 2.07–1.87 (m, 4H),1.78–1.73 (m, 2H), 1.56–1.53 (m, 1H), 1.35–1.19 (m, 8H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3204, 2931, 2858, 2667, 2570, 1611,1597, 1537, 1450, 1390, 1364, 1199, 1107, 1067, 1032, 1002, 967, 952,786.

Mass spectrum (FAB⁺) m/z: 320 ((M+H)⁺; as free form of title compound).

Example 21(2R)-2-Amino-2-methyl-4-[5-(4-phenyloxybutanoyl)furan-2-yl]butan-1-olfumarate (Exemplification compound number: 1-1199 having formula Ia-1)(21a)(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-[5-(4-phenyloxybutanoyl)furan-2-yl]butane

To a solution of(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(furan-2-yl)butane (0.2589 g,1.02 mmol) obtained in Reference example (5b) and 4-phenyloxybutanoylchloride (0.2446 g, 1.23 mmol) in dichloromethane (9.0 ml) was addeddropwise a solution of tin chloride (IV) in n-heptane (1.0 mmol/l)(2.0.5 ml, 2.05 mmol) at −78° C. over a 5-minute interval with stirringunder a nitrogen atmosphere, and the resulting mixture was furthermorestirred at the same temperature for 2 hours. After stirring, saturatedaqueous sodium hydrogencarbonate solution was added to the reactionmixture with stirring at the same temperature to quench the reaction,and then the temperature of the reaction mixture was raised to roomtemperature.

Subsequently, the reaction mixture was diluted with ethyl acetate, andinsoluble materials were filtered off. The filtrate was extracted withethyl acetate, and the extract was washed successively with water andsaturated aqueous sodium chloride solution and dried over anhydroussodium sulfate. After filtration, the solvent was removed in vacuo, andthe residue was purified by chromatography on a silica gel column usinga mixed solvent of ethyl acetate and hexane (2:1–1:0) as the eluent toafford the title compound (0.1483 g, yield: 35%)

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 7.29–7.25 (m, 2H), 7.13 (d, 1H,J=3.3 Hz), 7.00–6.87 (m, 3H), 6.18 (d, 1H, J=3.3 Hz), 5.42 (br s, 1H),4.30 (d, J=11.2 Hz), 4.15 (d, 1H, J=11.2 Hz), 4.04 (t, 2H, J=6.0 Hz),3.00 (t, 2H, J=7.2 Hz), 2.75–2.68 (m, 2H), 2.38–2.30 (m, 1H), 2.26–2.17(m, 2H), 2.10 (s, 3H), 2.07–2.1.99 (m, 1H), 1.94 (s, 3H), 1.34 (s, 3H).

Mass spectrum (FAB⁺) m/z: 416 ((M+H)⁺).

(21b)(2R)-2-Amino-2-methyl-4-[5-(4-phenyloxybutanoyl)furan-2-yl]butan-1-olfumarate

To a solution of(2R)-1-acetoxy-2-acetylamino-2-methyl-4-[5-(4-phenyloxybutanoyl)furan-2-yl]butane(0.2031 g, 0.49 mmol) obtained in Example (21a) in a mixed solvent oftetrahydrofuran (1.0 ml) and methanol (1.0 ml) were added successivelywater (1.0 ml) and lithium hydroxide monohydrate (0.2065 g, 4.92 mmol),and the resulting mixture was stirred at 50° C. for 4 hours. Aftercooling, water was added to the reaction mixture, and the resultingmixture was extracted with dichloromethane. The extract was washed withsaturated aqueous sodium chloride solution and dried over anhydroussodium sulfate. After filtration, the solvent was removed in vacuo, andthe residue was purified by chromatography on a basic silica gel column(NH type) using a mixed solvent of dichloromethane and methanol (100:1)as the eluent to afford the crude(2R)-2-amino-2-methyl-4-[5-(4-phenyloxybutanoyl)furan-2-yl]butan-1-ol(58.4 mg).

Subsequently, to a solution of the crude product thus obtained inmethanol (1.7 ml) was added fumaric acid (20.1 mg, 0.17 mmol), and theresulting mixture was stirred at room temperature for 30 minutes. Afterstirring, the reaction mixture was evaporated in vacuo, and ethylacetate was added to the residue. The crystals precipitated werecollected by filtration, washed with ethyl acetate and dried in vacuo toafford the title compound (61.5 mg, yield: 29%).

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 7.33 (d, 1H, J=3.4 Hz), 7.26–7.21(m, 2H), 6.91–6.84 (m, 3H), 6.35 (d, 1H, J=3.4 Hz), 6.25 (s, 2H), 4.03(t, 2H, J=6.0 Hz), 3.60 (d, J=11.7 Hz), 3.51 (d, 1H, J=11.7 Hz), 3.01(t, 2H, J=7.2 Hz), 2.88–2.75 (m, 2H), 2.18–1.95 (m, 4H), 1.30 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3112, 3038, 2961, 1671, 1583, 1517,1498, 1386, 1357, 1245, 1081, 1039, 869, 757, 719, 693.

Mass spectrum (FAB⁺) m/z: 332 ((M+H)⁺; as free form of title compound),

Elemental analysis (% as C₁₉H₂₅NO₄.C₄H₄O₄)

Calculated: C, 61.73; H, 6.53; N, 3.13. Found: C, 61.57; H, 6.40; N,2.93.

Example 22(2R)-2-Amino-2-methyl-4-{5-[3-(4-chlorophenyloxy)prop-1-ynyl]furan-2-yl}butan-1-oloxalate (Exemplification compound number: 1-1831 having formula Ia-1)(22a)(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-[5-(3-hydoxyprop-1-ynyl)furan-2-yl]butane

To a suspension of(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(5-iodofuran-2-yl)butane (1.5900g, 4.19 mmol) obtained in Reference example 7, 3-propyn-1-ol (0.73 ml,12.54 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.2940 g,0.42 mmol) and copper(I) iodide (0.161 g, 0.85 mmol) inN,N-dimethylformamide (42 ml) was added triethylamine (5.85 ml, 42.9mmol) with stirring, and the resulting mixture was stirred at 60° C.under a nitrogen atmosphere for 2 hours. After stirring, saturatedaqueous ammonium chloride solution was added to the reaction mixture toquench the reaction, and furthermore water and ethyl acetate were added.The resulting mixture was stirred at room temperature for 30 minutes andthen extracted with ethyl acetate. The extract was dried over anhydroussodium sulfate. After filtration, the solvent was removed in vacuo, andthe residue was purified by chromatography on a silica gel column usinga mixed solvent of ethyl acetate and hexane (2:1–1:0) to afford thetitle compound (1.0748 g, yield: 83%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 6.50 (d, 1H, J=3.2 Hz), 6.01 (d, 1H,J=3.2 Hz), 5.39 (br s, 1H), 4.50 (s, 2H), 4.29 (d, 1H, J=11.3 Hz), 4.16(d, 1H, J=11.3 Hz), 2.70–2.60 (m, 2H), 2.32–2.24 (m, 1H), 2.10 (s, 3H),2.03–1.95 (m, 1H), 1.94 (s, 3H), 1.77 (br s, 1H), 1.34 (s, 3H).

Mass spectrum (FAB⁺) m/z: 308 ((M+H)⁺).

(22b)(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-[5-(3-bromoprop-1-ynyl)furan-2-yl]butane

To a solution of(2R)-1-acetoxy-2-acetylamino-2-methyl-4-[5-(3-hydroxyprop-1-ynyl)furan-2-yl]butane(0.9515 g, 3.10 mmol) obtained in Example (22a) and triphenylphosphine(1.2375 g, 3.73 mmol) in dichloromethane (15 ml) was added carbontetrabromide (1.0545 g, 4.02 mmol) with stirring under ice-cooling, andthe resulting mixture was stirred at the same temperature for 30minutes. After stirring, methanol (0.2 ml) was added to the reactionmixture at the same temperature to quench the reaction, and then thetemperature of the reaction mixture was raised to room temperature.

Subsequently, the resulting mixture was evaporated in vacuo, and theresidue was purified by chromatography on a silica gel column using amixed solvent of dichloromethane and acetone (9:1) as the eluent toafford the title compound (0.9278 g, yield: 82%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 6.54 (d, 1H, J=3.0 Hz), 6.02 (d, 1H,J=3.0 Hz), 5.37 (br s, 1H), 4.29 (d, 1H, J=11.0 Hz), 4.18 (s, 2H), 4.16(d, 1H, J=11.0 Hz), 2.69–2.60 (m, 2H), 2.32–2.24 (m, 1H), 2.10 (s, 3H),2.02–1.95 (m, 1H), 1.94 (s, 3H), 1.34 (s, 3H).

(22c)(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-{5-[3-(4-chlorophenyloxy)prop-1-ynyl]furan-2-yl}butane

To a suspension of sodium hydride (content: 60%) (40.0 mg, 1.00 mmol) inN,N-dimethylformamide (4 ml) was added 4-chlorophenol (0.1302 g, 1.01mmol) with stirring under ice-cooling, and the resulting mixture wasstirred at room temperature for 30 minutes.

Subsequently, to the reaction mixture was added a solution of(2R)-1-acetoxy-2-acetylamino-2-methyl-4-[5-(3-bromoprop-1-ynyl)furan-2-yl]butane(0.3050 g, 0.82 mmol) obtained in Example (22b) in N,N-dimethylformamide(4 ml) with stirring under ice-cooling, and then the resulting mixturewas stirred at room temperature for 30 minutes. After stirring,saturated aqueous ammonium chloride solution was added to the reactionmixture to quench the reaction, and then the reaction mixture wasdiluted with water and ethyl acetate and extracted with ethyl acetate.The extract was washed successively with water and saturated aqueoussodium chloride solution and dried over anhydrous sodium sulfate. Afterfiltration, the solvent was removed in vacuo, and the residue waspurified by chromatography on a silica gel column using a mixed solventof dichloromethane and acetone (10:1) as the eluent to afford the titlecompound (0.3188 g, yield: 93%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 7.28–7.25 (m, 2H), 6.96–6.92 (m,2H), 6.52 (d, 1H, J=3.4 Hz), 6.01 (d, 1H, J=3.4 Hz), 5.36 (br s, 1H),4.90 (s, 2H), 4.29 (d, 1H, J=11.3 Hz), 4.15 (d, 1H, J=11.3 Hz),2.67–2.59 (m, 2H), 2.31–2.24 (m, 1H), 2.09 (s, 3H), 2.02–1.94 (m, 1H),1.93 (s, 3H), 1.34 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (CHCl₃) δ: 3444, 2225, 1738, 1681, 1511, 1491,1450, 1373, 1286, 1249, 1173, 1093, 1039, 1014, 824.

Mass spectrum (FAB⁺) m/z: 418 ((M+H)⁺).

(22d)(2R)-2-Amino-2-methyl-4-{5-[3-(4-chlorophenyloxy)prop-1-ynyl]furan-2-yl}butan-1-oloxalate

To a solution of(2R)-1-acetoxy-2-acetylamino-2-methyl-4-{5-[3-(4-chlorophenyloxy)prop-1-ynyl]furan-2-yl}butane(0.3083 g, 0.74 mmol) obtained in Example (22c) in a mixed solvent oftetrahydrofuran (1.5 ml) and methanol (1.5 ml) were added successivelywater (1.5 ml) and lithium hydroxide monohydrate (0.3096 g, 7.38 mmol),and the resulting mixture was stirred at 50° C. for 4 hours. Aftercooling, water was added to the reaction mixture, and the resultingmixture was extracted with dichloromethane. The extract was washed withsaturated aqueous sodium chloride solution and dried over anhydroussodium sulfate. After filtration, the solvent was removed in vacuo, andthe residue was purified by chromatography on a basic silica gel column(NH type) using a mixed solvent of dichloromethane and methanol (50:1)as the eluent to afford the crude(2R)-2-amino-2-methyl-4-{5-[3-(4-chlorophenyloxy)prop-1-ynyl]furan-2-yl}butan-1-ol(0.2156 g).

Subsequently, to a solution of the crude product thus obtained inmethanol (6.4 ml) was added anhydrous oxalic acid (98% pure) (59.1 mg,0.64 mmol), and the resulting mixture was stirred at room temperaturefor 30 minutes. After stirring, the reaction mixture was evaporated invacuo, and acetone was added to the residue. The crystals precipitatedwere collected by filtration, washed with acetone and dried in vacuo toafford the title compound (0.2307 g, yield: 75%).

¹H-NMR spectrum-(CD₃OD, 400 MHz) δ: 7.30–7.26 (m, 2H), 7.01–6.97 (m,2H), 6.57 (d, 1H, J=3.2 Hz), 6.14 (d, 1H, J=3.2 Hz), 4.96 (s, 2H), 3.58(d, 1H, J=11.7 Hz), 3.50 (d, 1H, J=11.7 Hz), 2.79–2.66 (m, 2H),2.07–1.89 (m, 2H), 1.28 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3401, 3120, 2979, 2925, 2228, 1725,1615, 1547, 1492, 1373, 1234, 1217, 1200, 1086, 1044, 1016, 830, 795,698, 506.

Mass spectrum (FAB⁺) m/z: 334 ((M+H)⁺; as free form of title compound).

Example 23(2R)-2-Amino-2-methyl-4-{5-[3-(3-trifluoromethylphenyloxy)prop-1ynyl]furan-2-yl}butan-1-oloxalate (Exemplification compound number: 1-1838 having formula Ia-1)

The title compound was synthesized in a yield of 76% using(2R)-1-acetoxy-2-acetylamino-2-methyl-4-[5-(3-bromoprop-1-ynyl)furan-2-yl]butaneobtained in Example (22b) and (3-trifluoromethyl)phenol as the startingmaterials by conducting successively the reactions similar to thosementioned in Examples (22c) and (22d).

¹H-NMR spectrum (DMSO-d₆, 400 MHz) δ: 7.60–7.55 (m, 1H), 7.36–7.53 (m,3H), 6.77 (d, 1H, J=3.3 Hz), 6.21 (d, 1H, J=3.3 Hz), 5.21 (s, 2H), 3.43(d, 1H, J=11.3 Hz), 3.37 (d, 1H, J=11.3 Hz), 2.67 (t, 2H, J=8.6 Hz),1.91–1.76 (m, 2H), 1.15 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3126, 2980, 2220, 1719, 1614, 1593,1546, 1455, 1328, 1207, 1167, 1130.

Mass spectrum (FAB⁺) m/z: 368 ((M+H)⁺; as free form of title compound),336.

Example 24(2R)-2-Amino-2-methyl-4-{5-[3-(3,4-dimethoxyphenyloxy)prop-1-ynyl]furan-2-yl}butan-1-oloxalate (Exemplification compound number: 1-1842 having formula Ia-1)

The title compound was synthesized in a yield of 68% using(2R)-1-acetoxy-2-acetylamino-2-methyl-4-[5-(3-bromoprop-1-ynyl)furan-2-yl]butaneobtained in Example (22b) and 3,4-dimethoxyphenol as the startingmaterials by conducting successively the reactions similar to thosementioned in Examples (22c) and (22d).

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 6.87 (d, 1H, J=8.8 Hz), 6.66 (d, 1H,J=2.9 Hz), 6.57–6.52 (m, 2H), 6.14 (d, 1H, J=3.6 Hz), 4.90 (s, 2H), 3.81(s, 3H), 3.78 (s, 3H), 3.59 (d, 1H, J=11.5 Hz), 3.50 (d, 1H, J=11.5 Hz),2.79–2.66 (m, 2H), 2.08–1.88 (m, 2H), 1.29 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3393, 3093, 2969, 2224, 1722, 1598,1537, 1513, 1467, 1452, 1278, 1260, 1228, 1194, 1157, 1135, 1021, 796,721, 698.

Mass spectrum (FAB⁺) m/z: 360 ((M+H)⁺; as free form of title compound).

Example 25(2R)-2-Amino-2-ethyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]butan-1-oloxalate (Exemplification compound number: 1-1660 having formula Ia-1)(25a)(2R)-1-Acetoxy-2-acetylamino-2-ethyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]butane

To a suspension of(2R)-1-acetoxy-2-acetylamino-2-ethyl-4-(5-iodofuran-2-yl)butane (79.1mg, 0.357 mmol) obtained in Reference example 18,4-cyclohexyloxybut-1-yne (168.2 mg, 1.10 mmol),dichlorobis(triphenylphosphine)palladium(II) (25.1 mg, 0.036 mmol) andcopper(I) iodide (13.8 mg, 0.072 mmol) in N,N-dimethylformamide (3.6 ml)was added triethylamine (0.5 ml, 0.36 mmol), and the resulting mixturewas stirred at 80° C. under a nitrogen atmosphere for 4 hours. Afterstirring, saturated aqueous ammonium chloride solution was added to thereaction mixture to quench the reaction, and furthermore water and ethylacetate were added. The resulting mixture was stirred at roomtemperature for 30 minutes. After stirring, the reaction mixture wasextracted with ethyl acetate. The extract was washed successively withwater and saturated aqueous sodium chloride solution and dried overanhydrous sodium sulfate. After filtration, the solvent was removed invacuo, and the residue was purified by chromatography on a silica gelcolumn using a mixed solvent of hexane and ethyl acetate (1:1–1:2) asthe eluent to afford the crude product (68.4 mg). The crude productobtained was furthermore purified using a preparative reversed phaseHPLC column [TSK-GEL ODS-80 Ts (2.0 cm×25 cm), TOSO, mobile phase:acetonitrile/water (70:30)] to afford the title compound (46.5 mg,yield: 31%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 6.38 (d, 1H, J=3.3 Hz), 5.96 (d, 1H,J=3.3 Hz), 5.27 .(br s, 1H), 4.28 (s, 2H), 3.65 (t, 2H, J=7.3 Hz),3.33–3.26 (m, 1H), 2.68 (t, 2H, J=7.3 Hz), 2.59 (t, 2H, J=8.4 Hz),2.20–2.13 (m, 1H), 2.08 (s, 3H), 2.05–1.98 (m, 1H), 1.94 (s, 3H), 1.90(m, 1H), 1.84–1.70 (m, 5H), 1.64 (m, 1H), 1.34–1.18 (m, 5H), 0.87 (t,3H, J=7.3 Hz).

IR spectrum ν_(max) cm⁻¹ (CDCl₃) δ: 3307, 3078, 2934, 2858, 2220, 1744,1658, 1540, 1452, 1369, 1237, 1103, 1042, 788, 756.

Mass spectrum (FAB⁺) m/z: 418 ((M+H)⁺).

(25b)(2R)-2-Amino-2-ethyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]butan-1-oloxalate

To a solution of(2R)-1-acetoxy-2-acetylamino-2-ethyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]butaneobtained in Example (25a) in a mixed solvent of tetrahydrofuran (0.5ml), methanol (0.5 ml) and water (0.5 ml) was added lithium hydroxidemonohydrate (44.7 mg, 1.07 mmol) with stirring, and the resultingmixture was stirred at 50° C. for 4 hours. After cooling, water wasadded to the reaction mixture, and the resulting mixture was extractedwith dichloromethane. The extract was washed with saturated aqueoussodium chloride solution and dried over anhydrous sodium sulfate. Afterfiltration, the solvent was removed in vacuo, and the residue waspurified by chromatography on a basic silica gel column (NH type) usinga mixed solvent of dichloromethane and methanol (1:0–50:1) as the eluentto afford the crude(2R)-2-amino-2-ethyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]butan-1-ol(35.3 mg, yield: 99%).

Subsequently, to a solution of the crude product thus obtained inmethanol was added anhydrous oxalic acid (98% pure) (9.5 mg, 0.106mmol), and the resulting mixture was stirred at room temperature for 30minutes. After stirring, the reaction mixture was evaporated in vacuo,and isopropyl ether was added to the residue. The crystals precipitatedwere collected by filtration, washed with isopropyl ether and dried invacuo to afford the title compound (39.9 mg, yield: 89%).

¹H-NMR spectrum (DMSO-d₆, 400 MHz) δ: 6.56 (d, 1H, J=3.3 Hz), 6.16 (d,1H, J=3.3 Hz), 4.19 (br s, 3H), 3.55 (t, 2H, J=6.7 Hz), 3.44 (s, 2H),3.33–3.28 (m, 1H), 2.67–2.60 (m, 4H), 1.83–1.79 (m, 4H), 1.66–1.55 (m,4H), 1.53–1.46 (m, 1H), 1.25–1.20 (m, 5H), 0.86 (t, 3H, J=7.5 Hz).

IR spectrum ν_(max) cm⁻¹ (KBr): 3402, 2931, 1918, 1611, 1542, 1198,1106, 1089, 721, 700.

Mass spectrum (FAB⁺) m/z: 356 ((M+Na)⁺), 334 ((M+H)⁺; as free form oftitle compound).

Example 26 Mono (2R)-2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]-1-butyl phosphate (Exemplification compound number: 5-1072having formula IIa-1) (26a)(2R)-2-Allyloxycarbonylamino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]butan-1-ol

To a suspension of(2R)-2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]butan-1-ol(0.5305 g, 1.66 mmol) obtained in Example 20 in a mixed solvent of ethylacetate (16 ml) and water (16 ml) were added potassium hydrogencarbonate(0.1995 g, 1.99 mmol) first and then allyl chloroformate (0.21 ml, 1.98mmol) with stirring, and the resulting mixture was stirred at roomtemperature for 30 minutes. After stirring, the reaction mixture wasdiluted with ethyl acetate and extracted with ethyl acetate. The extractwas washed with saturated aqueous sodium chloride solution and driedover anhydrous sodium sulfate. After filtration, the solvent was removedin vacuo to afford the title compound (0.6202 g, yield: 93%)

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 6.38 (d, 1H, J=3.0 Hz), 5.97 (d, 1H,J=3.0 Hz), 5.96–5.86 (m, 1H), 5.30 (ddd, 1H, J=17.6 Hz, 2.9 Hz, 1.5 Hz),5.22 (dt, 1H, J=9.5 Hz, 1.5 Hz), 4.82 (br s, 1H), 4.52 (br d, J=5.1 Hz),3.73–3.62 (m, 4H), 3.51 (br s, 1H), 3.33–3.26 (m, 1H), 2.74–2.58 (m,4H), 2.13 (ddd, 1H, J=13.9 Hz, 11.0 Hz, 5.1 Hz), 1.97–1.89 (m, 3H),1.75–1.72 (m, 2H), 1.56–1.51 (m, 1H), 1.34–1.18 (m, 8H).

(26b)(2R)-2-Allyloxycarbonylamino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]-1-butyl diallyl phosphate

To a solution of(2R)-2-allyloxycarbonylamino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]butan-1-ol(0.6202 g, 1.54 mmol) obtained in Example (26a) in dichloromethane (15ml) were added successively 1H-tetrazole (0.7220 g, 10.31 mmol) anddiallyl diisopropylphosphoramidite (0.81 ml, 3.06 mmol) with stirringunder ice-cooling, and then the reaction mixture was stirred at roomtemperature for 2 hours. After stirring, to the reaction mixture wasadded m-chloroperbenzoic acid (content: 70%) (0.7556 g, 3.07 mmol) withstirring under ice cooling, and the resulting mixture was stirred at thesame temperature for 10 minutes. After stirring, to the reaction mixturewas added 10% aqueous sodium thiosulfate solution to quench thereaction, and the resulting mixture was extracted with dichloromethane.The extract was washed successively with saturated aqueous sodiumhydrogencarbonate solution and saturated aqueous sodium chloridesolution and dried over anhydrous sodium sulfate. After filtration, thesolvent was removed in vacuo, and the residue was purified bychromatography on a silica gel column using a mixed solvent of hexaneand ethyl acetate (3:2) as the eluent to afford the title compound(0.7049 g, yield: 81%)

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 6.37 (d, 1H, J=3.0 Hz), 5.99–5.85(m, 3H), 5.40–5.19 (m, 6H), 4.87 (br s, 1H), 4.16 (dd, 1H, J=10.3 Hz,5.9 Hz), 4.03 (dd, 1H, J=10.3 Hz, 5.9 Hz), 3.65 (d, 2H, J=7.3 Hz),3.33–3.26 (m, 1H), 2.70–2.59 (m, 4H), 2.22–2.14 (m, 1H), 1.96–1.88 (m,3H), 1.75–1.72 (m, 2H), 1.56–1.53 (m, 1H), 1.34–1.22 (m, 8H).

Mass spectrum (FAB⁺) m/z: 563 (M⁺).

(26c) Mono(2R)-2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]-1-butylphosphate

To a suspension of(2R)-2-allyloxycarbonylamino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]-1-butyldiallyl phosphate (0.7037 g, 1.25 mmol) obtained in Example (26b),triphenylphosphine (69.0 mg, 0.26 mmol) andtetrakis(triphenylphosphine)palladium(0) (75.8 mg, 0.066 mmol) inacetonitrile (13 ml) was added pyrrolidine (0.66 ml, 7.91 mmol) withstirring under a nitrogen atmosphere, and the resulting mixture wasstirred at room temperature for 15 hours. After stirring, the reactionmixture was evaporated in vacuo, and the residue was diluted with 50%aqueous ethanol (40 ml) and then adjusted to pH 4 with acetic acid. Thecrystals precipitated were collected by filtration and washedsuccessively with water and ethanol to afford the crude product. Thecrude product thus obtained was dissolved in a mixed solvent of methanol(300 ml) and water (60 ml) under heating and treated with charcoal.After filtration, the filtrate was evaporated in vacuo, and to theresidue was added ethanol. The crystals precipitated were collected byfiltration, washed with ethanol and dried to afford the title compound(0.2672 g, yield: 54%).

¹H-NMR spectrum (CD₃CO₂D, 400 MHz) δ: 6.42 (d, 1H, J=3.7 Hz), 6.09 (d,1H, J=3.7 Hz), 4.10 (d, 2H, J=10.3 Hz), 3.70 (t, 2H, J=7.3 Hz),3.43–3.37 (m, 1H), 2.83–2.72 (m, 2H), 2.69 (t, 2H, J=7.3 Hz), 2.18–2.06(m, 2H), 1.94 (br d, 2H, J=10.3 Hz), 1.76–1.73 (m, 2H), 1.56–1.52 (m,1H), 1.40 (s, 3H), 1.38–1.18 (m, 5H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3413, 2931, 2857, 1645, 1566, 1540,1469, 1449, 1212, 1184, 1102, 1067, 1043, 949, 796, 511.

Mass spectrum (ESI⁻) m/z: 398 ((M−H)³¹ ).

Example 27 Mono(2R)-2-amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]-1-butylphosphate (Exemplification compound number: 5-824 having formula IIa-1)

The title compound was synthesized in a yield of 24% using(2R)-2-amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]butan-1-oloxalate obtained in Example 2 as the starting material by conductingsuccessively the reactions similar to those mentioned in Examples (26a),(26b) and (26c).

¹H-NMR spectrum (CD₃CO₂D, 400 MHz) δ: 6.39 (d, 1H, J=3.7 Hz), 6.07 (d,1H, J=3.7 Hz), 4.10 (d, 2H, J=10.3 Hz), 2.79–2.75 (m, 2H), 2.40 (t, 2H,J=7.3 Hz), 2.17–2.05 (m, 2H), 1.75–1.44 (m, 7H), 1.41 (s, 3H), 1.35–1.12(m, 6H), 0.95–0.90 (m, 2H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3233, 2922, 2850, 2559, 1642, 1594,1537, 1448, 1256, 1184, 1078, 1029, 942, 825, 794, 572, 514.

Mass spectrum (FAB⁻) m/z: 396 ((M−H)⁻).

Example 28 Mono(2R)-2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenyloxy)prop-1-ynyl]furan-2-yl}-1-butylphosphate (Exemplification compound number: 5-2278 having formula IIa-1)

The title compound was synthesized in a yield of 21% using(2R)-2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenyloxy)prop-1-ynyl]furan-2-yl}butan-1-oloxalate obtained in Example 4 as the starting material by conductingsuccessively the reactions similar to those mentioned in Examples (26a),(26b) and (26c).

¹H-NMR spectrum (CD₃CO₂D, 400 MHz) δ: 7.02 (d, 1H, J=8.1 Hz), 6.78 (d,1H, J=2.9 Hz), 6.73 (dd, 1H, J=8.1 Hz, 3.0 Hz), 6.56 (d, 1H, J=3.7 Hz),6.13 (d, 1H, J=3.7 Hz), 4.90 (s, 2H), 4.10 (d, 2H, J=10.3 Hz), 2.84–2.72(m, 2H), 2.22 (s, 3H), 2.17 (s, 3H), 2.15–2.05 (m, 2H), 1.40 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3411, 2922, 2227, 1616, 1536, 1501,1451, 1371, 1286, 1250, 1202, 1185, 1166, 1045, 1028, 931, 799, 573,514.

Mass spectrum (FAB⁻) m/z: 406 ((M−H)⁻).

Example 29(3R)-3-amino-3-methyl-5-[5-(5-phenylpentanoyl)furan-2-yl]pentylphosphonicacid (Exemplification compound number: 5-1344 having formula IIIa-1)(29a)(2R)-2-t-Butoxycarbonylamino-2-methyl-4-[5-(5-phenylpentanoyl)furan-2-yl]butan-1-ol

To a solution of(2R)-2-amino-2-methyl-4-[5-(5-phenylpentanoyl)furan-2-yl]butan-1-ol(97.8 mg, 0.30 mmol) obtained in Example 5 in dichloromethane (3 ml)were added successively di-t-butyl dicarbonate (77.3 mg, 0.35 mmol) andtriethylamine (85 μl, 0.61 mmol) with stirring, and the resultingmixture was stirred at room temperature for 19 hours. After stirring,the reaction mixture was evaporated in vacuo, and water was added to theresidue, and then the resulting mixture was extracted with ethylacetate. The extract was washed with saturated aqueous sodium chloridesolution and dried over anhydrous magnesium sulfate. After filtration,the solvent was removed in vacuo, and the residue was purified bychromatography on a silica gel column using a mixed solvent of hexaneand ethyl acetate (1:1) as the eluent to afford the title compound(112.2 mg, yield: 88%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 7.29–7.23 (m, 2H), 7.19–7.15 (m,3H), 7.08 (d, 1H, J=3.7 Hz), 6.18 (d, 1H, J=3.7 Hz), 4.63 (br s, 1H),4.03 (br s, 1H), 3.66 (d, 2H, J=5.9 Hz), 2.84–2.68 (m, 4H), 2.65 (t, 2H,J=8.1 Hz), 2.18 (ddd, 1H, J=16.6 Hz, 11.0 Hz, 5.1 Hz), 1.98 (ddd, 1H,J=16.6 Hz, 11.7 Hz, 5.1 Hz), 1.81–1.65 (m, 4H), 1.43 (s, 9H), 1.19 (s,3H).

Mass spectrum (FAB⁺) m/z: 430 ((M+H)⁺).

(29b)(2R)-2-t-Butoxycarbonylamino-2-methyl-4-[5-(5-phenylpentanoyl)furan-2-yl]-1-butanal

To a solution of(2R)-2-t-butoxycarbonylamino-2-methyl-4-[5-(5-phenylpentanoyl)furan-2-yl]butan-1-ol(110.2 mg, 0.26 mmol) obtained in Example (29a) in dichloromethane (2.6ml) was added Dess-Martin reagent (165.0 mg, 2.28 mmol), and theresulting mixture was stirred at room temperature under a nitrogenatmosphere for 1 hour. After stirring, the reaction mixture wasevaporated in vacuo, and to the residue was added a 10% aqueous sodiumthiosulfate solution to decompose the excess reagent. The resultingmixture was extracted with dichloromethane, and the extract was washedsuccessively with saturated aqueous sodium hydrogencarbonate solutionand saturated aqueous sodium chloride solution and dried over anhydrousmagnesium sulfate. After filtration, the solvent was removed in vacuo,and the residue was purified by chromatography on a silica gel columnusing a mixed solvent of hexane and ethyl acetate (3:1) as the eluent toafford the title compound (105.9 mg, yield: 97%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 9.34 (s, 1H), 7.29–7.25 (m, 2H),7.19–7.15 (m, 3H), 7.06 (d, 1H, J=3.6 Hz), 6.16 (d, 1H, J=3.6 Hz), 5.16(br s, 1H), 2.77 (t, 2H, J=7.3 Hz), 2.74–2.56 (m, 4H), 2.40–2.36 (m,1H), 2.22–2.14 (m, 1H), 1.80–1.65 (m, 4H), 1.44 (s, 9H), 1.37 (s, 3H).

Mass spectrum (FAB⁺) m/z: 428 ((M+H)⁺).

(29c) Diethyl(3R)-3-t-butoxycarbonylamino-3-methyl-5-[5-(5-phenylpentanoyl)furan-2-yl]pent-1-enylphosphonate

To a suspension of sodium hydride (content: 60%) (16.0 mg, 0.40 mmol) intetrahydrofuran (1 ml) was added tetraethyl methylenediphosphonate(0.100 ml, 0.40mmol) with stirring under ice-cooling over a 5-minuteinterval, and then the resulting mixture was stirred at room temperaturefor 1 hour.

Subsequently, to the reaction mixture was added a solution of diethyl(2R)-2-t-butoxycarbonylamino-2-methyl-4-[5-(5-phenylpentanoyl)furan-2-yl]-1-butanal(104.5 mg, 0.24 mmol) obtained in Example (29b) in tetrahydrofuran (4ml) with stirring under ice-cooling over a 5-minute interval, and theresulting mixture was stirred at the same temperature for 15 minutes.After stirring, the reaction mixture was neutralized with acetic acid(22 μl, 0.38 mmol) and evaporated in vacuo. Water was added to theresidue obtained, and the resulting mixture was extracted with ethylacetate. The extract was washed successively with water and saturatedaqueous sodium chloride solution and dried over anhydrous magnesiumsulfate. After filtration, the solvent was removed in vacuo, and theresidue was purified by chromatography on a silica gel column usingethyl acetate as the eluent to afford the title compound (129.0 mg,yield: 94%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 7.29–7.24 (m, 2H), 7.19–7.15 (m,3H), 7.07 (d, 1H, J=3.7 Hz), 6.75 (dd, 1H, J=22.7 Hz, 17.6 Hz), 6.16 (d,1H, J=3.7 Hz), 5.71 (t, 1H, J=17.6 Hz), 4.60 (br s, 1H), 4.15–4.04 (m,4H), 2.77 (t, 2H, J=8.1 Hz), 2.74–2.63 (m, 4H), 2.30–2.22 (m, 1H),2.09–2.01 (m, 1H), 1.81–1.65 (m, 4H), 1.42 (s, 9H), 1.40 (s, 3H), 1.33(t, 6H, J=7.3 Hz).

Mass spectrum (FAB⁺) m/z: 562 ((M+H)⁺).

(29d) Diethyl(3R)-3-t-butoxycarbonylamino-3-methyl-5-[5-(5-phenylpentanoyl)furan-2-yl]pentylphosphonate

To a solution of diethyl(3R)-3-t-butoxycarbonylamino-3-methyl5-[5-(5-phenylpentanoyl)furan-2-yl]pent-1-enylphosphonate(127.8 mg, 0.23 mmol) obtained in Example (29c) in ethanol (2.3 ml) wasadded chlorotris(triphenylphosphine)rhodium(I) (22.0 mg, 0.024 mmol),and the resulting mixture was stirred at 50° C. under a hydrogenatmosphere for 8 hours. After cooling, to the reaction mixture wasfurthermore added chlorotris(triphenylphosphine)rhodium(I) (21.5 mg,0.023 mmol), and the resulting mixture was stirred at 50° C. under ahydrogen atmosphere for 8 hours. After stirring, the reaction mixturewas evaporated in vacuo, and the residue was purified by chromatographyon a silica gel column using ethyl acetate as the eluent to afford thecrude product (142.1 mg). Furthermore, the crude product obtained waspurified using a preparative reversed phase HPLC column [Inertsil ODS-3(2.0 cm×25 cm), GL Science, mobile phase: acetonitrile/water (75:25),flow rate: 10 ml/min] to afford the title compound (109.5 mg, yield:85%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 7.29–7.25 (m, 2H), 7.19–7.15 (m,3H), 7.07 (d, 1H, J=3.7 Hz), 6.15 (d, 1H, J=3.7 Hz), 4.36 (br s, 1H),4.15–4.10 (m, 4H), 2.77 (t, 2H, J=7.3 Hz), 2.72–2.63 (m, 4H), 2.22–2.17(m, 2H), 1.92–1.85 (m, 1H), 1.80–1.63 (m, 7H), 1.42 (s, 9H), 1.33 (t,6H, J=7.3 Hz), 1.19 (s, 3H).

Mass spectrum (FAB⁺) m/z: 564 ((M+H)⁺).

(29e)(3R)-3-Amino-3-methyl-5-[5-(5-phenylpentanoyl)furan-2-yl]pentylphosphonicacid

To a solution of diethyl(3R)-3-t-butoxycarbonylamino-3-methyl-5-[5-(5-phenylpentanoyl)furan-2-yl]pentylphosphonate(108.2 mg, 0.19mmol) obtained in Example (29d) in dichloromethane (1.9ml) was added bromotrimethylsilane (0.255 ml, 1.93 mmol), and theresulting mixture was stirred at room temperature under a nitrogenatmosphere for 4 hours. After stirring, the reaction mixture wasevaporated in vacuo, and the residue was diluted with aqueous ethanol,and then the resulting mixture was adjusted to pH 4 with aqueous ammoniaand acetic acid. The crystals precipitated were collected by filtration,washed successively with water and ethanol and dried to afford the titlecompound (51.4 mg, yield: 66%).

¹H-NMR spectrum (CD₃CO₂D, 400 MHz) δ: 7.29 (d, 1H, J=3.7 Hz), 7.26–7.23(m, 2H), 7.18–7.12 (m, 3H), 6.35 (d, 1H, J=3.7 Hz), 2.85 (t, 4H, J=7.3Hz), 2.64 (t, 2H, J=7.3 Hz), 2.23–1.92 (m, 6H), 1.78–1.64 (m, 4H), 1.44(s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3160, 2934, 2860, 2560, 2529, 1670,1552, 1516, 1453, 1391, 1314, 1140, 1068, 1046, 913, 882, 804, 723, 700,568, 525, 490, 468.

Mass spectrum (FAB⁻) m/z: 406 ((M−H)⁻).

Example 30(2R)-2-Amino-2-methyl-4-[1-methyl-5-(5-phenylbut-1-ynyl)pyrrol-2-yl]butan-1-ol½ oxalate (Exemplification compound number: 1-559 having formula Ia-2)

The title compound was synthesized in a yield of 58% using(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(1-methyl-5-iodopyrrol-2-yl)butaneobtained in Reference example 13 and 4-phenylbut-1-yne as the startingmaterials by conducting successively the reactions similar to thosementioned in Examples (1a) and (1b).

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 7.30–7.26 (m, 4H), 7.21–7.16 (m,1H), 6.09. (d, 1H, J=3.7 Hz), 5.76 (d, 1H, J=3.7 Hz), 3.59 (d, 1H,J=11.7 Hz), 3.52 (d, 1H, J=11.7 Hz), 3.41 (s, 3H), 2.88 (t, 2H, J=7.3Hz), 2.73 (t, 2H, J=7.3 Hz), 2.62–2.58 (m, 2H), 1.98–1.80 (m, 2H), 1.29(s, 3H). IR spectrum ν_(max) cm⁻¹ (KBr): 3362, 3026, 2943, 2224, 2080,1591, 1496, 1454, 1300, 1073.

Mass spectrum (FAB⁺) m/z: 311 ((M+H)⁺; as free form of title compound).

Example 31(2R)-2-Amino-2-methyl-4-[1-methyl-5-(5-phenylpentyl)pyrrol-2-yl]butan-1-ol½ oxalate (Exemplification compound number: 1-93 having formula Ia-2)(31a)(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]butane

To a suspension of(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(1-methyl-5-iodopyrrol-2-yl)butane(0.2918 g, 0.74 mmol) obtained in Reference example 13,5-phenylpent-1-yne (0.3225 g, 2.24 mmol),dichlorobis(triphenylphosphine)palladium(II) (52.3 mg, 0.075 mmol) andcopper(I) iodide (29.0 mg, 0.15 mmol) in N,N-dimethylformamide (7.4 ml)was added triethylamine (1.04 ml, 7.5 mmol) with stirring, and theresulting mixture was stirred at room temperature under a nitrogenatmosphere for 1 hour. After stirring, saturated aqueous ammoniumchloride solution was added to the reaction mixture to quench thereaction, and furthermore water and ethyl acetate were added. Theresulting mixture was stirred at room temperature for 30 minutes. Afterstirring, the reaction mixture was extracted with ethyl acetate, and theextract was washed successively with water and saturated aqueous sodiumchloride solution and dried over anhydrous sodium sulfate. Afterfiltration, the solvent was removed in vacuo, and the residue waspurified by chromatography on a silica gel column using a mixed solventof ethyl acetate and hexane. (3:2) as the eluent to afford the titlecompound (0.2205 g, yield: 73%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 7.31–7.27 (m, 2H), 7.22–7.18 (m,3H), 6.26 (d, 1H, J=3.7 Hz), 5.81 (d, 1H, J=3.7 Hz), 5.35 (br s, 1H),4.32 (d, 1H, J=11.3 Hz), 4.18 (d, 1H, J=11.3 Hz), 3.55 (s, 3H), 2.78 (t,2H, J=7.7 Hz), 2.55 (t, 2H, J=8.2 Hz), 2.46 (t, 2H, J=7.0 Hz), 2.27–2.19(m, 1H), 2.09 (s, 3H), 1.97–1.84 (m, 6H), 1.37 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (CHCl₃): 3443, 2944, 2861, 1736, 1679, 1603,1512, 1454, 1374, 1251, 1042.

Mass spectrum (FAB⁺) m/z: 409 ((M+H)⁺), 408(M⁺).

(31b)(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-[1-methyl-5-(5-phenylpentyl)pyrrol-2-yl]butane

To a solution of(2R)-1-acetoxy-2-acetylamino-2-methyl-4-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]butane(77 mg, 0.19 mmol) obtained in Example (31a) in methanol (2 ml) wasadded 10% palladium-charcoal (50% wet with water) (4.3 mg), and theresulting mixture was stirred at room temperature under a hydrogenatmosphere for 1 hour. After stirring, the internal atmosphere wasreplaced with nitrogen, and the palladium-charcoal in the reactionmixture was filtered off using celite, which was washed with ethylacetate. The filtrate and the washings were combined and evaporated todryness in vacuo to afford the title compound (75.5 mg, yield: 97%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 7.28–7.25 (m, 2H), 7.18–7.15 (m,3H), 5.79 (d, 1H, J=3.7 Hz), 5.77 (d, 1H, J=3.7 Hz), 5.36, (br s, 1H),4.32 (d, 1H, J=11.0 Hz), 4.19 (d, 1H, J=11.0 Hz), 3.37 (s, 3H), 2.61 (t,2H, J=7.7 Hz), 2.55–2.47 (m, 4H), 2.23–2.15 (m, 1H), 2.07 (s, 3H),1.94–1.87 (m, 1H), 1.90 (s, 3H), 1.70–1.59 (m, 4H), 1.53 (s, 3H),1.47–1.39 (m, 2H).

Mass spectrum (FAB⁺) m/z: 412 ((M+H)⁺).

(31c)(2R)-2-Amino-2-methyl-4-[1-methyl-5-(5-phenylpentyl)pyrrol-2-yl]butan-1-ol½ oxalate

To a solution of(2R)-1-acetoxy-2-acetylamino-2-methyl-4-[1-methyl-5-(5-phenylpentyl)pyrrol-2-yl]butane(75.0 mg, 0.18 mmol) obtained in Example (31b) in a mixed solvent oftetrahydrofuran (1 ml) and methanol (1 ml) were added successively water(1 ml) and lithium hydroxide monohydrate (76 mg, 1.81 mmol) withstirring, and the resulting mixture was stirred at 50° C. for 6 hours.After cooling, water was added to the reaction mixture, and theresulting mixture was extracted with dichloromethane. The extract waswashed with saturated aqueous sodium chloride solution and dried overanhydrous sodium sulfate. After filtration, the solvent was removed invacuo, and the residue was purified by chromatography on a basic silicagel column (NH type) using a mixed solvent of dichloromethane andmethanol (1:0–50:1) as the eluent to afford(2R)-2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentyl)pyrrol-2-yl]butan-1-ol(53.6 mg, yield: 90%).

Subsequently, to a solution of(2R)-2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentyl)pyrrol-2-yl]butan-1-ol(53.6 mg) thus obtained in methanol (1.6 ml) was added anhydrous oxalicacid (98% pure) (7.4 mg, 0.082 mmol), and the resulting mixture wasstirred at room temperature for 1 hour. After stirring, the reactionmixture was evaporated in vacuo, and ethyl acetate was added to theresidue. The crystals precipitated were collected by filtration, washedwith ethyl acetate and dried in vacuo to afford the title compound (49.2mg, yield: 81%).

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 7.25–7.21 (m, 2H), 7.16–7.11 (m,3H), 5.71 (d, 1H, J. =3.7 Hz), 5.66 (d, 1H, J=3.7 Hz), 3.60 (d, 1H,J=11.7 Hz), 3.52 (d, 1H, J=11.7 Hz), 3.41 (s, 3H), 2.65–2.56 (m, 4H),2.53–2.49 (m, 2H), 1.99–1.81 (m, 2H), 1.68–1.56 (m, 4H), 1.44–1.37 (m,2H), 1.30 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3315, 2930, 2092, 1632, 1591, 1549,1455, 1304, 1073.

Mass spectrum (FAB⁺) m/z: 329 ((M+H)⁺; as free form of title compound).

Example 32(2R)-2-Amino-2-methyl-4-[1-methyl-5-(4-phenylbutyl)pyrrol-2-yl]butan-1-ol½ oxalate (Exemplification compound number: 1-31 having formula Ia-2)

The title compound was synthesized in a yield of 28% using(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(1-methyl-5-iodopyrrol-2-yl)butaneobtained in Reference example 13 and 4-phenylbut-1-yne as the startingmaterials by conducting successively the reactions similar to thosementioned in Examples (31a), (31b) and (31c).

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 7.25–7.21 (m, 2H), 7.16–7.11 (m,3H), 5.71 (d, 1H, J=2.9 Hz), 5.66 (d, 1H, J=2.9 Hz), 3.60 (d, 1H,J.=11.7 Hz), 3.53 (d, 1H, J=11.7 Hz), 3.39 (s, 3H), 2.66–2.53 (m, 6H),1.98–1.81 (m, 2H), 1.72–1.55 (m, 4H), 1.30 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3347, 3024, 2933, 2858, 1589, 1454,1299, 1072, 763, 745, 698.

Mass spectrum (FAB⁺) m/z: 315 ((M+H)⁺; as free form of title compound).

Example 33(2R)-2-Amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-olhydrochloride (Exemplification compound number: 1-1093 having formulaIa-2) (33a)(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-{1-methyl-[5-phenyl-1-(5-phenylpentanoyloxy)pent-1-enyl]pyrrol-2-yl}butane

To a solution of(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(1-methylpyrrol-2-yl)butane(4.23 g, 15.4 mmol) obtained in Reference example (19b) in toluene (100ml) was added a solution of 4-dimethylaminopyridine (9.41 g, 77.0 mmol)and 5-phenylvaleroyl chloride (98%) (7.92 g, 39.5 mmol) in toluene (50ml), and the resulting mixture was stirred at 110° C. for 48 hours.After cooling to room temperature, ethyl acetate and water were added tothe reaction mixture, and the resulting mixture was extracted with ethylacetate. The extract was washed successively with water and saturatedaqueous sodium chloride solution and dried over anhydrous sodiumsulfate. After filtration, the solvent was removed in vacuo, and theresidue was purified by chromatography on a silica gel column using amixed solvent of ethyl acetate and hexane (3:2–2:1) as the eluent toafford the title compound (4.03 g, yield: 45%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 7.26–7.23 (m, 4H), 7.17–7.11 (m,6H), 6.96(d, 1H, J=4.2 Hz), 5.97 (d, 1H, J=4.2 Hz), 5.41 (br s, 1H),4.31 (d, 1H, J=11.0 Hz), 4.15 (d, 1H, J=11.0 Hz), 4.11 (t, 1H, J=8.1Hz), 3.83 (s, 3H), 2.67–2.39 (m, 8H), 2.34–2.26 (m, 1H), 2.10 (s, 3H),2.04–1.86 (m, 6H), 1.61–1.48 (m, 6H), 1.36 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (CHCl₃): 3443, 2938, 2861, 1733, 1681, 1634,1487, 1454, 1374, 1249, 1044.

Mass spectrum (FAB⁺) m/z: 587 ((M+H)⁺).

(33b)(2R)-2-Amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-olhydrochloride

To a solution of(2R)-1-acetoxy-2-acetylamino-2-methyl-4-{1-methyl-[5-phenyl-1-(5-phenylpentanoyloxy)pent-1-enyl]pyrrol-2-yl}butane(4.0270 g, 6.86 mmol) obtained in Example (33a) in a mixed solvent oftetrahydrofuran (14 ml) and methanol (14 ml) were added successivelywater (14 ml) and lithium hydroxide monohydrate (2.8820 g, 68.68 mmol),and the resulting mixture was stirred at 50° C. for 4 hours. Aftercooling, water was added to the reaction mixture, and the resultingmixture was extracted with dichloromethane. The extract was washed withsaturated aqueous sodium chloride solution and dried over anhydroussodium sulfate. After filtration, the solvent was removed in vacuo, andthe residue was purified by chromatography on a basic silica gel column(NH type) using a mixed solvent of dichloromethane and methanol (100:1)as the eluent to afford the crude(2R)-2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol(2.1152 g).

Subsequently, to a solution of the crude product thus obtained inmethanol (31 ml) was added 4N hydrochloric acid-dioxane solution (1.54ml, 6.16 mmol), and the resulting mixture was stirred at roomtemperature for 10 minutes. After stirring, the reaction mixture wasevaporated in vacuo, and ethyl acetate was added to the residue. Thecrystals precipitated were collected by filtration, washed with ethylacetate and dried in vacuo to afford the title compound (2.0685 g,yield: 79%).

Melting point: 130–131° C.,

Angle of rotation: [α]_(D)=−4.81 (c=1.00, MeOH), ¹H-NMR spectrum (CD₃₀D,400 MHz) δ: 7.25–7.21 (m, 2H), 7.17–7.11 (m, 3H), 7.05 (d, 1H, J=4.2Hz), 6.03 (d, 1H, J=4.2 Hz), 3.86 (s, 3H), 3.65 (d, 1H, J=11.4 Hz), 3.55(d, 1H, J=11.4 Hz), 2.78–2.67 (m, 4H), 2.63 (t, 2H, J=7.2 Hz), 2.02(ddd, 1H, J=13.8 Hz, 9.4 Hz, 7.6 Hz), 1.90 (ddd, 1H, J=13.8 Hz, 11.5 Hz,6.3 Hz), 1.70–1.64 (m, 4H), 1.34 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3215, 2937, 2883, 2691, 2571, 1646,1525, 1482, 1457, 1380, 1294, 1228, 1182, 1055, 998, 913, 770, 751, 700.

Mass spectrum (FAB⁺) m/z: 343 ((M+H)⁺; as free form of title compound),

Elemental analysis (% as C₂₁H₃₀N₂O₂.HCl)

Calculated: C, 66.56; H, 8.25; N, 7.39; Cl; 9.36. Found C: 66.51; H,8.20; N, 7.47; Cl; 9.08.

Example 34(2R)-2-Amino-2-methyl-4-{1-methyl-5-[5-(4-fluorophenyl)pentanoyl]pyrrol-2-yl}butan-1-olhydrochloride (Exemplification compound number: 1-1094 having formulaIa-2)

The title compound was synthesized in a yield of 42% using(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(1-methylpyrrol-2-yl)butaneobtained in Reference example (19b) and 5-(4-fluorophenyl)valeroylchloride as the starting materials by conducting successively thereactions similar to those mentioned in Examples (33a) and (33b).

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 7.20–7.13 (m, 2H), 7.05 (d, 1H,J=4.0 Hz), 6.99–6.92 (m, 2H), 6.03 (d, 1H, J=4.0 Hz), 3.86 (s, 3H), 3.65(d, 1H, J=11.4 Hz), 3.55 (d, 1H, J=11.4 Hz), 2.76 (t, 2H, J=7.3 Hz),2.74–2.66 (m, 2H), 2.62 (t, 2H, J=7.3 Hz), 2.08–1.86 (m, 2H), 1.73–1.60(m, 4H), 1.35 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3352, 3210, 3153, 3035, 2930, 2863,1634, 1601, 1509, 1480, 1464, 1371, 1349, 1222, 1175, 1067, 823, 766.

Mass spectrum (FAB⁺) m/z:361 ((M+H)⁺; as free form of title compound).

Example 35(2R)-2-Amino-2-methyl-4-[1-methyl-5-(4-phenylbutanoyl)pyrrol-2-yl]butan-1-olhydrochloride (Exemplification compound number: 1-1082 having formulaIa-2)

The title compound was synthesized in a yield of 48% using(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(1-methylpyrrol-2-yl)butaneobtained in Reference example (19b) and 4-phenylbutyryl chloride as thestarting materials by conducting successively the reactions similar tothose mentioned in Examples (33a) and (33b).

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 7.28–7.12 (m, 5H), 6.97 (d, 1H,J=4.0 Hz), 6.02 (d, 1H, J=4.0 Hz), 3.86 (s, 3H), 3.65 (d, 1H, J=11.7Hz), 3.55 (d, 1H, J=11.7. Hz), 2.78–2.62 (m, 6H), 2.08–1.85 (m, 4H),1.35 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3203, 3025, 2941, 2572, 2029, 1649,1518, 1482, 1457, 1382, 1297, 1179, 1140, 1057, 989, 915, 752, 699.

Mass spectrum (FAB⁺) m/z: 329 ((M+H)⁺; as free form of title compound).

Example 36(2R)-2-Amino-2-methyl-4-[1-methyl-5-(3-phenylpropanoyl)pyrrol-2-yl]butan-1-olhydrochloride (Exemplification compound number: 1-1080 having formulaIa-2)

The title compound was synthesized in a yield of 42% using(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(1-methylpyrrol-2-yl)butaneobtained in Reference example (19b) and 3-phenylpropionyl chloride asthe starting materials by conducting successively the reactions similarto those mentioned in Examples (33a) and (33b).

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 7.27–7.11 (m, 5H), 7.03 (d, 1H,J=4.4 Hz), 6.01 (d, 1H, J=4.4 Hz), 3.86 (s, 3H), 3.65 (d, 1H, J=11.7Hz), 3.55 (d, 1H, J=11.7 Hz.), 3.09–3.02 (m, 2H), 2.99–2.92 (m, 2H),2.76–2.62 (m, 2H), 2.08–1.85 (m, 2H), 1.34 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3376, 3026, 2932, 2559, 1640, 1605,1484, 1455, 1410, 1381, 1294, 1225, 1135, 1069, 983, 924, 770, 747, 699.

Mass spectrum (FAB⁺) m/z: 315 ((M+H)⁺; as free form of title compound).

Example 37(2R)-2-Amino-2-methyl-4-[1-methyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]butan-1-olhydrochloride (Exemplification compound number: 1-1083 having formulaIa-2)

The title compound was synthesized in a yield of 29% using(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(1-methylpyrrol-2-yl)butaneobtained in Reference example (19b) and 5-cyclohexylvaleroyl chloride asthe starting materials by conducting successively the reactions similarto those mentioned in Examples (33a) and (33b).

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 7.05 (d, 1H, J=4.0 Hz), 6.04 (d, 1H,J=4.0. Hz), 3.87 (s, 3H), 3.65 (d, 1H, J=11.7 Hz), 3.55 (d, 1H, J=11.7Hz), 2.78–2.64 (m, 4H), 2.09–1.86 (m, 2H), 1.76–1.58 (m, 7H), 1.40–1.10(m, 11H), 0.95–0.80 (m, 2H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3354, 3212, 3156, 3034, 2921, 2850,1637, 1498, 1480, 1464, 1379, 1370, 1292, 1224, 1175, 1066, 1054, 914,762.

Mass spectrum (FAB⁺) m/z: 349 ((M+H)⁺; as free form of title compound).

Example 38(2R)-2-Amino-2-methyl-4-[1-methyl-4-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol½ oxalate (Exemplification compound number: 2-252 having formula Ib-2)(38a)(4R)-4-Methyl-4-{2-[1-methyl-4-(5-phenylpentanoyl)pyrrol-2-yl]ethyl}-1,3-oxazolidin-2-one

To a solution of(4R)-4-methyl-4-[2-(1-methylpyrrol-2-yl)ethyl]-1,3-oxazolidin-2-one (100mg, 0.48 mmol) obtained in Reference example 11 in benzene (4 ml) wereadded successively N,N-dimethyl-5-phenylpentanamide (99 mg, 0.48 mmol)and phosphoryl chloride (43 μl, 0.46 mmol), and the resulting mixturewas refluxed for 6 hours. After refluxing, to the reaction mixture wasadded 20% aqueous sodium acetate solution (2 ml), and the resultingmixture was stirred at 80° C. for 15 minutes. After cooling to roomtemperature, water was added to the reaction mixture, and the resultingmixture was extracted with ethyl acetate. The extract was washedsuccessively with water and saturated aqueous sodium chloride solutionand dried over anhydrous magnesium sulfate. After filtration, thesolvent was removed in vacuo, and the residue was purified bychromatography on a silica gel column using a mixed solvent of ethylacetate and hexane (1:1–3:2–4:1) as the eluent to afford the titlecompound (11 mg, yield: 6%)

¹H-NMR spectrum (CDCl₃, 500 MHz) δ: 7.30–7.24 (m, 2H), 7.20–7.15 (m,4H), 6.31 (s, 1H), 5.72 (br s, 1H), 4.17 (d, 1H, J=8.6 Hz), 4.10 (d, 1H,J=8.6 Hz), 3.57 (s, 3H), 2.70–2.55 (m, 6H), 1.94 (t, 2H, J=8.2 Hz),1.78–1.60 (m, 4H), 1.43 (s, 3H).

Mass spectrum (FAB⁺) m/z: 369 ((M+H)⁺).

(38b)(2R)-2-Amino-2-methyl-4-[1-methyl-4-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol½ oxalate

To a solution of(4R)-4-methyl-4-{2-[1-methyl-4-(5-phenylpentanoyl)pyrrol-2-yl]ethyl}-1,3-oxazolidin-2-one(11 mg, 0.03 mmol) obtained in Example (38a) in a mixed solvent oftetrahydrofuran (1 ml) and methanol (1 ml) was added a 5N aqueouspotassium hydroxide solution (1 ml), and the resulting mixture wasrefluxed for 2 days. After cooling, water was added to the reactionmixture, and the resulting mixture was extracted with dichloromethane.The extract was dried over anhydrous sodium sulfate. After filtration,the solvent was removed in vacuo to afford the crude product of(2R)-2-amino-2-methyl-4-[1-methyl-4-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol(9 mg).

Subsequently, to a solution of the crude product (6.5 mg) thus obtainedin methanol (0.5 ml) was added anhydrous oxalic acid (98% pure) (0.85mg, 0.0095 mmol), and the resulting mixture was stirred at roomtemperature for 10 minutes. After stirring, the reaction mixture wasconcentrated to dryness to afford the title compound (7.0 mg, yield:84%).

¹H-NMR spectrum (CD₃OD, 500 MHz) δ: 7.42 (s, 1H), 7.26–7.20 (m, 2H),7.17–7.11 (m, 3H), 6.32 (s, 1H), 3.65–3.60 (m, 4H), 3.57 (d, 1H, J=11.7Hz), 2.74–2.60 (m, 6H), 2.04–1.86 (m, 2H), 1.73–1.62 (m, 4H), 1.33 (s,3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3339, 3025, 2929, 2859, 2565, 1611,1525, 1497, 1453, 1438, 1355, 1310, 1176, 1069, 928, 818, 774, 749, 700.

Mass spectrum (FAB⁺) m/z: 343 ((M+H)⁺; as free form of title compound).

Example 39(2R)-2-Amino-2-methyl-4-[1-methyl-5-(5-phenyl-1-hydroxypentyl)pyrrol-2-yl]butan-1-ol½ oxalate (Exemplification compound number: 1-1399 having formula Ia-2)

To a suspension of(2R)-2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-olhydrochloride (185 mg, 0.49 mmol) obtained in Example (33b) indichloromethane (10 ml) was added 1N aqueous sodium hydroxide solution,and the resulting mixture was stirred for 5 minutes. After stirring, thereaction mixture was extracted with dichloromethane, and the extract waswashed with saturated aqueous sodium chloride solution and dried overanhydrous sodium sulfate. After filtration, the solvent was removed invacuo to afford(2R)-2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol.

Subsequently, to a solution of(2R)-2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-olthus obtained in methanol (5 ml) was added sodium borohydride (28 mg,0.74 mmol) with stirring under ice-cooling, and then the resultingmixture was stirred at room temperature for 1 hour. After stirring, tothe reaction mixture was furthermore added sodium borohydride (28 mg,0.74 mmol), and the resulting mixture was stirred at room temperaturefor 20 hours. After stirring, to the reaction mixture was additionallyadded sodium borohydride (28 mg, 0.74 mmol), and the resulting mixturewas stirred at room temperature for 7 hours. After stirring, water wasadded to the reaction mixture, and the resulting mixture was extractedwith ethyl acetate. The extract was washed successively with water andsaturated aqueous sodium chloride solution and dried over anhydroussodium sulfate. After filtration, the filtrate was concentrated todryness in vacuo, and the residue was purified using a preparativereversed phase HPLC column [Inertsil ODS-3 (2.0 cm×25 cm), GL Science,mobile phase: acetonitrile/0.1% aqueous ammonium acetate solution(70:30), flow rate: 10 ml/min] to afford(2R)-2-amino-2-methyl-4-[1-methyl-5-(5-phenyl-1-hydroxypentyl)pyrrol-2-yl]butan-1-ol(79 mg).

Subsequently, to a solution of(2R)-2-amino-2-methyl-4-[1-methyl-5-(5-phenyl-1-hydroxypentyl)pyrrol-2-yl]butan-1-ol(79 mg, 0.23 mmol) thus obtained in methanol (2 ml) was added anhydrousoxalic acid (98% pure) (9.3 mg, 0.11 mmol), and the resulting mixturewas stirred at room temperature for 30 minutes. After stirring, thereaction mixture was concentrated to dryness in vacuo to afford thetitle compound (57 mg, yield: 30%)

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 7.25–7.20 (m, 2H), 7.17–7.09 (m,3H), 5.91 (d, 1H, J=3.4 Hz), 5.76 (d, 1H, J=3.4 Hz), 4.57 (t, 1H, J=6.6Hz), 3.59 (d, 1H, J=12.0 Hz), 3.54 (s, 3H), 3.53 (d, 1H, J=12.0 Hz),2.65–2.55 (m, 4H), 2.00–1.80 (m, 4H), 1.70–1.58 (m, 2H), 1.54–1.44 (m,1H), 1.43–1.32 (m, 1H), 1.30 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3212, 3026, 2935, 2897, 2571, 1719,1700, 1611, 1521, 1496, 1454, 1405, 1279, 1218, 1053, 767, 721, 700.

Mass spectrum (FAB⁺) m/z: 325 ((M+H)⁺; as free form of title compound).

Example 40(2R)-2-Amino-2-methyl-4-{5-[3-(2-cyclohexylethyloxy)phenyl]-1-methylpyrrol-2-yl}butan-1-ol½ oxalate (Exemplification compound number: 1-1444 having formula Ia-2)(40a)(4R)-4-Methyl-4-[2-(5-iodo-1-methylpyrrol-2-yl)ethyl]-1,3-oxazolidin-2-one

To a solution of(4R)-4-methyl-4-[2-(1-methylpyrrol-2-yl)ethyl]-1,3-oxazolidin-2-one(0.6187 g, 2.97 mmol) obtained in Reference example 11 intetrahydrofuran (30 ml) were added successively pyridine (1.2 ml, 14.9mmol) and iodine (1.5060 g, 5.93 mmol) with stirring under ice-cooling,and the resulting mixture was stirred at the same temperature for 10minutes. After stirring, to the reaction mixture was added 10% aqueoussodium thiosulfate solution to quench the reaction, and the reactionmixture was concentrated to about one-half of its initial volume, whichwas extracted with ethyl acetate. The extract was washed successivelywith saturated aqueous sodium hydrogencarbonate solution and saturatedaqueous sodium chloride solution and dried over anhydrous sodiumsulfate. After filtration, the filtrate was evaporated to dryness invacuo, and the residue was purified by chromatography on a silica gelcolumn using a mixed solvent of ethyl acetate and hexane (3:2) as theeluent to afford the title compound (0.6660 g, yield: 67%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 6.30 (d, 1H, J=3.7 Hz), 5.93 (d, 1H,J=3.7 Hz), 5.17 (br s, 1H), 4.15 (d, 1H, J=8.8 Hz), 4.09 (d, 1H, J=8.8Hz), 3.50 (s, 3H), 2.76–2.63 (m, 2H), 1.96–1.85 (m, 2H), 1.42 (s, 3H).

(40b)(4R)-4-Methyl-4-[2-{2-[3-(2-cyclohexylethyloxy)phenyl]-1-methylpyrrol-2-yl}ethyl]-1,3-oxazolidin-2-one

(4R)-4-Methyl-4-[2-(5-iodo-1-methylpyrrol-2-yl)ethyl]-1,3-oxazolidin-2-one(0.3101 g, 0.92 mmol) obtained in Example (40a),2-[3-(2-cyclohexylethyloxy)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane(0.4646 g, 1.41 mmol), dichlorobis(triphenylphosphine)palladium(II)(63.1 mg, 0.09 mmol) and cesium carbonate (0.6006 g, 1.81 mmol) weresuspended in a mixed solvent of dimethoxyethane (8 ml) and water (2 ml)and stirred at 80° C. for 6 hours. After cooling, water was added to thereaction mixture, and the resulting mixture was extracted with ethylacetate. The extract was washed successively with water and saturatedaqueous sodium chloride solution and dried over anhydrous magnesiumsulfate. After filtration, the solvent was removed in vacuo, and theresidue was purified by chromatography on a silica gel column using amixed solvent of ethyl acetate and hexane (3:2) as the eluent to affordthe crude product. Furthermore, the crude product thus obtained waspurified using a preparative reversed phase HPLC column [Inertsil ODS-3(2.0 cm×25 cm), GL Science, mobile phase: acetonitrile/water (75:25),flow rate: 10 ml/min] to afford the title compound (41.1 mg, yield:11%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 7.30–7.26 (m, 1H), 6.93–6.89 (m,2H), 6.85–6.83 (m, 1H), 6.14 (d, 1H, J=3.7 Hz), 5.95 (d, 1H, J=3.7 Hz),5.27 (br s, 1H), 4.18 (d, J=8.8 Hz), 4.10 (d, 1H, J=8.8 Hz), 4.01 (t,2H, J=6.6 Hz), 3.52 (s, 3H), 2.77–2.64 (m, 2H), 2.06–1.94 (m, 2H),1.78–1.64 (m, 6H), 1.55–1.46 (m, 1H), 1.45 (s, 3H), 1.31–1.11 (m, 4H),1.02–0.92 (m, 2H).

Mass spectrum (FAB⁺) m/z: 411 ((M+H)⁺).

(40c)(2R)-2-Amino-2-methyl-4-{5-[3-(2-cyclohexylethyloxy)phenyl]-1-methylpyrrol-2-yl}butan-1-ol½ oxalate

To a solution of(4R)-4-methyl-4-[2-{2-[3-(2-cyclohexylethyloxy)phenyl]-1-methylpyrrol-2-yl}ethyl]-1,3-oxazolidin-2-one(41.0 g, 0.10 mmol) obtained in Example (40b) in a mixed solvent oftetrahydrofuran (1 ml) and methanol (0.5 ml) was added a 5N aqueouspotassium hydroxide solution (0.5 ml), and the resulting mixture wasrefluxed for 4 days. After cooling, water was added to the reactionmixture, and the resulting mixture was extracted with dichloromethane.The extract was dried over anhydrous sodium sulfate. After filtration,the solvent was removed in vacuo, and the residue was purified bychromatography on a basic silica gel column (NH type) using a mixedsolvent of dichloromethane and methanol (50:1) as the eluent to afford(2R)-2-amino-2-methyl-4-{5-[3-(2-cyclohexylethyloxy)phenyl]-1-methylpyrrol-2-yl}butan-1-ol(36.5 mg).

Subsequently, to a solution of(2R)-2-amino-2-methyl-4-{5-[3-(2-cyclohexylethyloxy)phenyl]-1-methylpyrrol-2-yl}butan-1-ol(36.2 mg) thus obtained in methanol (1 ml) was added anhydrous oxalicacid (98% pure) (4.4 mg, 0.05 mmol), and the resulting mixture wasstirred at room temperature for 30 minutes. After stirring, the reactionmixture was evaporated in vacuo, and 2-propanol was added to theresidue. The crystals precipitated were collected by filtration, washedwith 2-propanol and dried in vacuo to afford the title compound (35.6mg, yield: 86%).

¹H-NMR spectrum (CD₃OD, 400 MHz) δ: 7.27 (t, 1H, J=8.1 Hz), 6.89 (d, 1H,J=8.1 Hz), 6.85–6.81 (m, 2H), 6.03 (d, 1H, J=3.7 Hz), 5.91 (d, 1H, J=3.7Hz), 4.02 (t, 1H, J=6.6 Hz), 3.63 (d, J=11.7 Hz), 3.56 (d, 1H, J=11.7Hz), 3.54 (s, 3H), 2.77–2.65 (m, 2H), 2.07–1.90 (m, 2H), 1.81–1.64 (m,7H), 1.59–1.47 (m, 1H), 1.34 (s, 3H), 1.32–1.15 (m, 3H), 1.05–0.95 (m,2H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3354, 2923, 2851, 1595, 1579, 1509,1463, 1301, 1211, 1066, 1049, 763, 698.

Mass spectrum (FAB⁺) m/z: 385 ((M+H)⁺; as free form of title compound).

Example 41(2R)-2-Amino-2-methyl-4-[1-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-olhydrochloride (Exemplification compound number: 4-12 having formulaIa-5) (41a)(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-{1-ethyl-[5-phenyl-1-(5-phenylpentanoyloxy)pent-1-enyl]pyrrol-2-yl}butane

To a solution of(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(1-ethylpyrrol-2-yl)butane (2.1g, 7.49 mmol) obtained in Reference example 24 in toluene (100 ml) wereadded 4-dimethylaminopyridine (4.58 g, 37.5 mmol) first and then asolution of 5-phenylvaleroyl chloride (4.4 g, 22.5 mmol) in toluene (20ml), and the resulting mixture was refluxed for 5 days. After cooling toroom temperature, water was added to the reaction mixture, and theresulting mixture was extracted with ethyl acetate. The extract waswashed successively with water and saturated aqueous sodium chloridesolution and dried over anhydrous sodium sulfate. After filtration, thefiltrate was concentrated to dryness in vacuo, and the residue waspurified by chromatography on a silica gel column using a mixed solventof hexane and ethyl acetate (4:6) as the eluent to afford the crudeproduct. Furthermore, the crude product thus obtained was purified usinga preparative reversed phase HPLC column [Inertsil ODS-3 (2.0 cm×25 cm),GL Science, mobile phase: acetonitrile/0.1% aqueous ammonium acetatesolution (70/30), flow rate: 10 ml/min] to afford the title compound(2.8 g, yield: 66%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 7.26–7.21 (m, 4H), 7.18–7.09 (m,6H), 6.98 (d, 1H, J=4.4 Hz), 5.97 (d, 1H, J=4.4 Hz), 5.43 (br s, 1H),4.35–4.28 (m, 1H), 4.33 (d, 1H, J: =11.0 Hz), 4.17 (d, 1H, J=11.0 Hz),4.12 (q, 2H, J=7.3 Hz), 2.65–2.25 (m, 9H), 2.10 (s, 3H), 2.07–1.86 .(m,3H), 1.96 (s, 3H), 1.62–1.47 (m, 6H), 1.37 (s, 3H), 1.25 (t, 3H, J=7.3Hz).

(41b)(2R)-2-Amino-2-methyl-4-[1-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-olhydrochloride

To a solution of(2R)-1-acetoxy-2-acetylamino-2-methyl-4-{1-ethyl-[5-phenyl-1-(5-phenylpentanoyloxy)pent-1-enyl]pyrrol-2-yl}butane(2.8 g, 4.66 mmol) obtained in Example (41a) in a mixed solvent ofmethanol (12 ml), tetrahydrofuran (12 ml) and water (12 ml) was addedlithium hydroxide monohydrate (1.96 g, 46.6 mmol) with stirring, and theresulting mixture was stirred at 50° C. for 5 hours. After cooling toroom temperature, water was added to the reaction mixture, and theresulting mixture was extracted with dichloromethane. The extract waswashed with saturated aqueous sodium chloride solution and dried overanhydrous sodium sulfate. After filtration, the solvent was removed invacuo, and the residue was purified by chromatography on a basic silicagel column (NH type) using a mixed solvent of dichloromethane andmethanol (100:1) as the eluent to afford the crude product of(2R)-2-amino-2-methyl-4-[1-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol(1.53 g).

Subsequently, to a solution of the crude product (1.53 g) obtained abovein ethanol (15 ml) was added 4N hydrochloric acid-dioxane solution (1.07ml, 4.26 mmol) with stirring under ice-cooling, and the resultingmixture was stirred at the same temperature for 30 minutes. Afterstirring, the reaction mixture was concentrated to dryness in vacuo, andthe crystals obtained were recrystallized from ethyl acetate to affordthe title compound (1.46 g, yield: 80%).

¹H-NMR spectrum (DMSO-D₆, 400 MHz) δ: 7.90 (br s, 2H), 7.29–7.24 (m,2H), 7.20–7.13 (m, 3H), 7.06 (d, 1H, J=4.0 Hz), 5.94 (d, 1H, J=4.0 Hz),5.53 (t, 1H, J=4.8 Hz), 4.29 (q, 2H, J=7.3 Hz), 3.49 (dd, 1H, J=11.0 Hz,4.8 Hz), 3.43. (dd, 1H, J=11.0 Hz, 4.8 Hz), 2.79–2.70 (m, 2H), 2.69–2.55(m, 4H), 1.94–1.88 (m, 2H), 1.64–1.53 (m, 4H), 1.22 (s, 3H), 1.17 (t,3H, J=7.3 Hz).

IR spectrum ν_(max) cm⁻¹ (KBr): 3377, 2936, 1639, 1479, 1393, 1068.

Mass spectrum (FAB⁺) m/z: 357 ((M+H)⁺; as free form of title compound).

Example 42(2R)-2-Amino-2-methyl-4-[5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol(Exemplification compound number: 3-12 having formula Ia-4) (42a)(4R)-4-Methyl-4-{2-[5-(5-phenylpentanoyl)pyrrol-2-yl]ethyl}-1,3-oxazolidin-2-one

To a solution of(4R)-4-methyl-4-[2-(pyrrol-2-yl)ethyl]-1,3-oxazolidine-2-one (138 mg,0.71 mmol) obtained in Reference example 28 in tetrahydrofuran (5 ml)was added a 3.0M solution of methylmagnesium bromide in ether (0.50 ml,1.49 mmol), and the resulting mixture was refluxed for 30 minutes. Aftercooling, to the reaction mixture was added a solution of5-phenylvaleroyl chloride (0.169 g, 22.5 mmol) in tetrahydrofuran (1 ml)at room temperature with stirring, and the resulting mixture wasrefluxed for 1 hour. After cooling to room temperature, water was addedto the reaction mixture, and the resulting mixture was extracted withethyl acetate. The extract was washed successively with water andsaturated aqueous sodium chloride solution and dried over anhydroussodium sulfate. After filtration, the filtrate was concentrated todryness in vacuo, and the residue was purified by chromatography on asilica gel column using a mixed solvent of ethyl acetate and hexane(2:1) as the eluent to afford the crude product. Furthermore, the crudeproduct obtained above was purified using a preparative reversed phaseHPLC column [Inertsil ODS-3 (2.0 cm×25 cm), GL Science, mobile phase:acetonitrile/water (70/30), flow rate: 20 ml/min] to afford the titlecompound (41 mg, yield: 16%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 9.67 (br s, 1H), 7.31–7.22 (m, 3H),7.20–7.13 (m, 2H), 6.85–6.78 (m, 1H), 6.03–5.96. (m, 1H), 5.70 (br s,1H), 4.16 (d, 1H, J=8.8 Hz), 4.07 (d, 1H, J==8.8 Hz), 2.80–2.67 (m, 4H),2.67–2.58 (m, 2H), 2.01–1.88 (m, 2H), 1.81–1.61 (m, 4H), 1.37 (s, 3H).

IR spectrum ν_(max cm) ⁻¹ (CHCl₃): 3442, 3271, 2935, 2861, 1758, 1632,1492, 1454, 1410, 1382, 1046, 940.

Mass spectrum (FAB⁺) m/z: 355 ((M+H)⁺).

(42b)(2R)-2-Amino-2-methyl-4-[5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol

To a solution of(4R)-4-methyl-4-{2-[5-(5-phenylpentanoyl)pyrrol-2-yl]ethyl}-1,3-oxazolidin-2-one(41.0 mg, 0.12 mmol) obtained in Example (42a) in a mixed solvent ofmethanol (2 ml), tetrahydrofuran (2 ml) and water (2 ml) was added 10Naqueous sodium hydroxide solution (0.12 ml, 1.17 mmol), and theresulting mixture was refluxed for 4 days. After cooling to roomtemperature, water was added to the reaction mixture, and the resultingmixture was extracted with ethyl acetate. The extract was washed withsaturated aqueous sodium chloride solution and dried over anhydroussodium sulfate. After filtration, the solvent was removed in vacuo, andthe residue was purified by chromatography on a basic silica gel column(NH type) using a mixed solvent of dichloromethane and methanol (20:1)as the eluent to afford the title compound (30.0 mg, yield: 79%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 9.90 (br s, 1H), 7.32–7.22 (m, 3H),7.20–7.12 (m, 2H), 6.79 (d, 1H, J=3.7 Hz), 5.98 (d, 1H, J=3.7 Hz), 3.40(d, 1H, J=10.3 Hz), 3.35 (d, 1H, J=10.3 Hz), 2.80–2.59 (m, 6H),2.01–1.62 (m, 6H), 1.11 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (CHCl₃): 3272, 2927, 2857, 1624, 1494, 1454,1410, 1363, 1293, 1263, 1210, 1048, 915, 801, 749, 700.

Mass spectrum (FAB⁺) m/z: 329 ((M+H)⁺).

Example 43 Mono(2R)-2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]-1-butylphosphate (Exemplification Compound number: 5-1344 having Formula IIa-2)(43a)(2R)-2-t-Butoxycarbonylamino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol

To a solution of(2R)-2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-olhydrochloride (1.4647 g, 3.87 mmol) obtained in Example (33b) indichloromethane (38 ml) were added successively di-t-butyl dicarbonate(1.0126 g, 4.64 mmol) and triethylamine (1.62 ml, 11.65 mmol) withstirring, and the resulting mixture was stirred at room temperature for18 hours. After stirring, the reaction mixture was evaporated in vacuo,and water was added to the residue, and then the resulting mixture wasextracted with ethyl acetate. The extract was washed with saturatedaqueous sodium chloride solution and dried over anhydrous magnesiumsulfate. After filtration, the solvent was removed in vacuo, and theresidue was purified by chromatography on a silica gel column using amixed solvent of hexane and ethyl acetate (3:2) as the eluent to affordthe title compound (1.6928 g, yield: 99%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 7.28–7.24 (m, 2H), 7.18–7.14 (m,3H), 6.90 (d, 1H, J=3.7 Hz), 5.95 (d, 1H, J=3.7 Hz), 4.63 (br s, 1H),3.98 (br s, 1H), 3.87 (s, 3H), 3.68 (d, 2H, J=6.6 Hz), 2.75 (t, 2H,J=7.3 Hz), 2.70–2.62 (m, 3H), 2.55 (ddd, 1H, J=15.4 Hz, 12.4 Hz, 5.1Hz), 2.13–2.04 (m, 1H), 1.96–1.89 (m, 1H), 1.79–1.64 (m, 4H), 1.43 (s,9H), 1.21 (s, 3H).

Mass spectrum (FAB⁺) m/z: 443((M+H)⁺).

(43b)(2R)-2-t-Butoxycarbonylamino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]-1-butyldiallyl phosphate

To a solution of(2R)-2-t-butoxycarbonylamino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol(1.6928 g, 3.83 mmol) obtained in Example (43a) in dichloromethane (19ml) were added successively 1H-tetrazole (1.7933 g, 25.60 mmol) anddiallyl diisopropylphosphoramidite (2.02 ml, 7.64 mmol) with stirringunder ice-cooling, and then the resulting mixture was stirred at roomtemperature for 2 hours. After stirring, to the reaction mixture wasadded a solution of t-butyl hydroperoxide in n-decane (5–6 mol/l) (2.3ml, 11.5 mmol) with stirring under ice cooling, and the resultingmixture was stirred at the same temperature for 15 minutes. Afterstirring, to the reaction mixture was added an aqueous sodium sulfitesolution to quench the reaction, and the resulting mixture was extractedwith dichloromethane. The extract was washed successively with saturatedaqueous sodium hydrogencarbonate solution and saturated aqueous sodiumchloride solution and dried over anhydrous sodium sulfate. Afterfiltration, the solvent was removed in vacuo, and the residue waspurified by chromatography on a silica gel column using a mixed solventof hexane and ethyl acetate (3:2) as the eluent to afford the titlecompound (1.5690 g, yield: 68%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 7.28–7.24 (m, 2H), 7.18–7.14 (m,3H), 6.89 (d, 1H, J=3.7 Hz), 5.99–5.89 (m, 3H), 5.39–5.29 (m, 4H), 4.62(br s, 1H), 4.60–4.52 (m, 4H), 4.21 (dd, 1H, J=9.5 Hz, 5.1 Hz), 4.01(dd, 1H, J=9.5 Hz, 5.9 Hz), 3.86 (s, 3H), 2.74 (t, 2H, J=7.3 Hz), 2.64(t, 2H, J=8.1 Hz), 2.58 (t, 2H, J=8.1 Hz), 2.22–2.12 (m, 1H), 1.90 –1.81(m, 1H), 1.79–1.64 (m, 4H), 1.43 (s, 9H), 1.26 (s, 3H).

Mass spectrum (FAB⁺) m/z.: 603((M+H)⁺).

(43c) Mono(2R)-2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]-1-butylphosphate

To a suspension of(2R)-2-t-butoxycarbonylamino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]-1-butyldiallyl phosphate (1.5665 g, 2.60 mmol) obtained in Example (43b),triphenylphosphine (0.1402 g, 0.54 mmol) andtetrakis(triphenylphosphine)palladium(0) (0.1503 g, 0.13 mmol) inacetonitrile (26 ml) was added pyrrolidine (1.1 ml, 13 mmol) withstirring under a nitrogen atmosphere, and the resulting mixture wasstirred at room temperature for 24 hours. After stirring, the reactionmixture was evaporated in vacuo, and 1N hydrochloric acid was added tothe residue, and then the resulting mixture was extracted withdichloromethane. The extract was dried over anhydrous sodium sulfate.After filtration, the filtrate was evaporated in vacuo to afford thecrude product (1.4625 g).

Subsequently, to a solution of the crude product (1.4625 g) thusobtained in dichloromethane (26 ml) was added trifluoroacetic acid (8.6ml) with stirring under ice-cooling. After the reaction temperature wasraised to room temperature, the resulting mixture was furthermorestirred at room temperature for 2 hours. The reaction mixture wasevaporated in vacuo, and ethanol was added to the residue. The crystalsprecipitated were collected by filtration to afford the crude crystals.The crude crystals obtained were dissolved in a mixed solvent ofmethanol (200 ml) and water (67 ml), treated with charcoal and filteredusing celite. The filtrate was evaporated in vacuo, and ethanol wasadded to the residue. The crystals precipitated were collected byfiltration; washed with ethanol and dried to afford the title compound(0.5554 g, yield: 51%).

¹H-NMR spectrum (CD₃CO₂D, 400 MHz) δ : 7.25–7.22 (m, 2H), 7.17–7.11 (m,3H), 7.07 (d, 1H, J=4.4 Hz), 6;04 (d, 1H, J=4.4 Hz), 4.17 (d, 2H, J=10.3Hz), 3.87 (s, 3H), 2.82–2.71 (m, 4H), 2.63 (t, 2H, J,=7.3 Hz), 2.20–2.01(m, 2H), 1.75–1.63 (m, 4H), 1.46 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3429, 2934, 2857, 2717, 2603, 1639,1557, 1480, 1455, 1378, 1182, 1056, 1041, 946, 915, 821, 748, 699, 580,511.

Mass spectrum (FAB⁻) m/z 421((M−H)⁻).

Example 44(3R)-3-Amino-3-methyl-5-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]pentylphosphonicacid (Exemplification compound number: 5–1344 having formula IIIa-2)(44a)(2R)-2-t-Butoxycarbonylamino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]-1-butanal

To a solution of(2R)-2-t-butoxycarbonylamino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol(0.3520 g, 0.80 mmol) obtained in Example (43a) in dichloromethane (8ml) were added successively molecular sieves 4A (0.2234 g) andpyridinium dichromate (0.4594 g, 1.22 mmol), and the resulting mixturewas stirred at room temperature for 20 hours. After stirring, ether wasadded to the reaction mixture, and the resulting mixture was filtered.The filtrate was evaporated in vacuo, and the residue was purified bychromatography on a silica gel column using a mixed solvent of hexaneand ethyl acetate (3:2) as the eluent to afford the title compound(0.2195 g, yield: 63%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 9.36 (s, 1H), 7.28–7.25 (m, 2H),7.18–7.15 (m, 3H), 6.89 (d, 1H, J=3.7 Hz), 5.92 (d, 1H, J=3.7 Hz), 5.20(br s, 1H), 3.83 (s, 3H), 2.74 (t, 2H, J=7.3 Hz), 2.64 (t, 2H, J=7.3Hz), 2.59–2.52 (m, 1H), 2.45–2.28 (m, 2H), 2.09–2.03 (m, 1H), 1.78–1.64(m, 4H), 1.44 (s, 9H), 1.40 (s, 3H).

(44b) Diethyl(3R)-3-t-butoxycarbonylamino-3-methyl-5-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]pent-1-enylphosphonate

To a suspension of sodium hydride (content: 60%) (31.0 mg, 0.78 mmol) intetrahydrofuran (1 ml) was added tetraethyl methylenediphosphonate(0.185 ml, 0.75 mmol) with stirring under ice-cooling over a 5-minuteinterval, and then the resulting mixture was stirred at room temperaturefor 30 minutes.

Subsequently, to the reaction mixture was added a solution of(2R)-2-t-butoxycarbonylamino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]-1-butanal(0.2155 g, 0.49 mmol) obtained in Example (44a) in tetrahydrofuran (4ml) with stirring under ice-cooling over a 5-minute interval, and theresulting mixture was stirred at the same temperature for 30 minutes.After stirring, the reaction mixture was neutralized with acetic acid(42 μl, 0.73 mmol) and evaporated in vacuo. Water was added to theresidue obtained, and the resulting mixture was extracted with ethylacetate. The extract was washed successively with water and saturatedaqueous sodium chloride solution and dried over anhydrous magnesiumsulfate. After filtration, the solvent was removed in vacuo, and theresidue was purified by chromatography on a silica gel column using amixed solvent of ethylacetate and hexane (2:1–1:0) as the eluent toafford the title compound (0.2348 g, yield: 85%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 7.28–7.25 (m, 2H), 7.18–7.15 (m,3H), 6.90 (d, 1H, J=4.4 Hz), 6.77 (dd, 1H, J=22.7 Hz, 17.6 Hz), 5.92 (d,1H, J=4.4 Hz), 5.72 (t, 1H, J=17.6 Hz), 4.59 (br s, 1H), 4.12–4.05 (m,4H), 3.84 (s, 3H), 2.74 (t, 2H, J=7.3 Hz), 2.64 (t, 2H, J 7.3 Hz),2.59–2.50 (m, 2H), 2.26–2.18 (m, 1H), 2.01–1.93 (m, 1H), 1.78–1.64 (m,4H), 1.42 (s, 12H), 1.32 (t, 6H, J=7.3 Hz).

Mass spectrum (FAB⁺) m/z: 575 ((M+H)⁺)

(44c) Diethyl(3R)-3-t-butoxycarbonylamino-3-methyl-5-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]pentylphosphonate

To a solution of diethyl(3R)-3-t-butoxycarbonylamino-3-methyl-5-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]pent-1-enylphosphonate(145.4 mg, 0.25 mmol) obtained in Example (44b) in ethanol (2.5 ml) wasadded chlorotris(triphenylphosphine)rhodium(I) (23.7 mg, 0.026 mmol),and the resulting mixture was stirred at 50° C. under a hydrogenatmosphere for 5 hours. After cooling, to the reaction mixture was addedfurthermore chlorotris(triphenylphosphine)rhodium(I) (24.3 mg, 0.026mmol), and the resulting mixture was stirred at 50° C. under a hydrogenatmosphere for 5 hours. After stirring, the reaction mixture wasevaporated in vacuo, and the residue was purified by chromatography on asilica gel column using ethyl acetate as the eluent to afford the crudeproduct (154.0 mg). Furthermore, the crude product obtained was purifiedusing a preparative reversed phase HPLC column [Inertsil ODS-3 (2.0cm×25 cm), GL Science, mobile phase: acetonitrile/water (80:20), flowrate: 10 ml/min] to afford the title compound (116.1 mg, yield: 80%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 7.28–7.24 (m, 2H), 7.18–7.14 (m,3H), 6.89 (d, 1H, J=3.7 Hz), 5.92 (d, 1H, J=3.7 Hz), 4.37 (br s, 1H),4.14–4.05 (m, 4H), 3.85 (s, 3H), 2.74 (t, 2H, J=7.3 Hz), 2.64 (t, 2H,J=7.3 Hz), 2.59–2.50 (m, 2H), 2.24–2.15 (m, 2H), 1.83–1.64 (m, 8H), 1.42(s, 9H), 1.33 (t, 3H, J=7.3 Hz), 1.32 (t, 3H, J=7.3 Hz), 1.21 (s, 3H).

Mass spectrum (FAB⁺) m/z: 577((M+H)⁺).

(44d)(3R)-3-Amino-3-methyl-5-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]pentylphosphonicacid

To a solution of diethyl(3R)-3-t-butoxycarbonylamino-3-methyl-5-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]pentylphosphonate(114.0 mg, 0.20 mmol) obtained in Example (44c) in dichloromethane (2.0ml) was added bromotrimethylsilane (0.26 ml, 1.97 mmol), and theresulting mixture was stirred at room temperature under a nitrogenatmosphere for 5 hours. After stirring, the reaction mixture wasevaporated in vacuo, and the residue was diluted with aqueous ethanoland then adjusted to pH 4 with aqueous ammonia and acetic acid. Thecrystals precipitated were collected by filtration, washed successivelywith water and ethanol and dried to afford the title compound (52.0 mg,yield: 63%).

¹H-NMR spectrum (CD₃CO₂D, 400 MHz) δ : 7.26–7.22 (m, 2H), 7.18–7.12 (m,3H), 7.07 (d, 1H, J=4.1 Hz), 6.05 (d, 1H, J=4.1 Hz), 3.88 (s, 3H), 2.80(t, 2H, J=7.3 Hz), 2.73 (t, 2H, J=8.8 Hz), 2.63 (t, 2H, J=7.3 Hz),2.23–1.94 (m, 6H), 1.76–1.64 (m, 4H), 1.48 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3171, 3025, 2936, 2859, 2549, 1640,1552, 1484, 1461, 1380, 1136, 1064, 1051, 914, 881, 772, 741, 699.

Mass spectrum (FAB⁻) m/z: 419((M−H)⁻).

Reference Example 1 (Furan-2-yl)methyl triphenylphosphonium bromide

To a solution of furfuryl alcohol (29.43 g, 300 mmol) in tetrahydrofuran(300 ml) was added a solution of phosphorus tribromide (10 ml, 105 mmol)in tetrahydrofuran (30 ml) with stirring under ice-cooling over a30-minute interval, and then the resulting mixture was stirred at roomtemperature for 1 hour. After stirring, the reaction mixture wasneutralized with aqueous sodium hydroxide solution [prepared bydissolving sodium hydroxide (30.23 g) in water (75 ml)], and the organiclayer was separated by partitioning, and dried with sodium hydroxide (10g) . The organic layer was collected by decantation, and to the organiclayer were added anhydrous sodium sulfate and charcoal, and then theresulting mixture was filtered.

Subsequently, to the filtrate were added tetrahydrofuran (150 ml) firstand then triphenylphosphine (78.64 g, 300 mmol) with stirring, and theresulting mixture was stirred at 70° C. for 2 hours. After cooling, thecrystals precipitated were collected by filtration, washed with ethylacetate and dried in vacuo to afford the title compound (98.84 g, yield:78%).

Reference Example 2(2R)-2-t-Butoxycarbonylamino-1-n-hexanoyloxy-2-methyl-4-(furan-2-yl)-3-butene(2a) (2R)-2-t-Butoxycarbonylamino-3-n-hexanoyloxy-2-methyl-1-propanol

To a suspension of 2-t-butoxycarbonylamino-2-methylpropane-1,3-diol(20.0 g, 97.4 mmol) in isopropyl ether (200 ml) were added successivelyvinyl hexanoate (16.3 ml, 0.10 mol) and lipase [Immobilized lipase fromPseudomonas sp., TOYOBO, 0.67 U/mg] (0.8 g) with stirring, and theresulting mixture was stirred at room temperature for 2 hours. Afterstirring, the reaction mixture was filtered and evaporated in vacuo. Theresidue obtained was purified by chromatography on a silica gel columnusing a mixed solvent of hexane and ethyl acetate (10:1–2:1) as theeluent to afford the title compound (25.0 g, yield: 85%).

Furthermore, the(2R)-2-t-butoxycarbonylamino-3-n-hexanoyloxy-2-methyl-1-propanolobtained above was analyzed with a HPLC column for separating opticalisomers [ChiralCel OF (0.46 cm×25 cm), Daicel Chemical Industries, Ltd.,mobile phase: hexane/2-propanol (70/30), flow rate: 0.5 ml/min], and itsoptical purity was determined.

From the results of the HPLC analysis, it was confirmed that thecompound eluted first (retention time: 8.2 min) was the 2S-isomer, andthe compound eluted afterward (retention time: 10.5 min) was the2R-isomer, and that the optical purity of the product synthesized was85% ee.

Angle of rotation : [α]D=−8.5 (c=1.86, CHCl₃), ¹H-NMR spectrum (CDCl₃,400 MHz) δ : 4.86 (s, 1H), 4.25 (d, 1H, J=11.2 Hz), 4.19 (d, 1H, J=11.2Hz), 3.86 (br s, 1H), 3.70–3.55(m, 2H), 2.36 (t, 2H, J=7.4 Hz), 1.44 (s,9H), 1.40–1.30 (m, 4H), 1.25 (s, 3H), 0.90 (t, 3H, J=7.0 Hz).

IR spectrum ν_(max) cm⁻¹ (Liquid Film): 3415, 3380, 2961, 2935, 2874,1721, 1505, 1458, 1392, 1368, 1293, 1248, 1168, 1076.

Mass spectrum (FAB⁺) m/z: 304((M+H)⁺).

(2b) (2S)-2-t-Butoxycarbonylamino-3-n-hexanoyloxy-2-methyl-1-propanal

To a solution of(2R)-2-t-butoxycarbonylamino-3-n-hexanoyloxy-2-methyl-1-propanol (30.70g, 0.101 mol) obtained in Reference example (2a) in dichloromethane (600ml) were added successively molecular sieves 4A (220 g) and pyridiniumchlorochromate (43.6 g, 0.202 mol) with stirring under ice-cooling, andthen the resulting mixture was stirred at room temperature for 2 hours.After stirring, ether was added to the reaction mixture, and afterfiltration, the filtrate was evaporated in vacuo. The residue obtainedwas purified by chromatography on a silica gel column using a mixedsolvent of hexane and ethyl acetate (10:1–5:1) as the eluent to affordthe title compound. (28.81 g, yield: 95%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 9.45 (s, 1H), 5.26 (br s, 1H), 4.44(d, 1H, J=11.2 Hz), 4.32 (d, 1H, J=11.2 Hz), 2.32 (t, 2H, J=7.46 Hz),1.70–1.55 (m, 2H), 1.45 (s, 9H), 1.38 (s, 3H), 1.40–1.25 (m, 4H), 0.90(t, 3H, J=7.0 Hz).

IR spectrum ν_(max) cm⁻¹ (Liquid Film): 3367, 2961, 2935, 2874, 1742,1707, 1509, 1458, 1392, 1369, 1290, 1274, 1254, 1166, 1100, 1078.

Mass spectrum (FAB⁺) m/z: 302((M+H)⁺).

(2c)(2R)-2-t-Butoxycarbonylamino-1-n-hexanoyloxy-2-methyl-4-(furan-2-yl)-3-butene

To a suspension of (furan-2-yl)methyl triphenylphosphonium bromide(33.65 g, 79.5 mmol) obtained in Reference example 1 in tetrahydrofuran(90 ml) was added a solution of potassium t-butoxide (8.94 g, 79.7 mmol)in tetrahydrofuran (90 ml) with stirring under ice-cooling over a10-minute interval, and the resulting mixture was furthermore stirredunder ice-cooling for 15 minutes.

Subsequently, to the reaction mixture was added a solution of(2S)-2-t-butoxycarbonylamino-3-n-hexanoyloxy-2-methyl-1-propanal (16.18g, 53.7 mmol) obtained in Reference example (2b) in tetrahydrofuran (60ml) with stirring under ice-cooling over a 15-minute interval, and theresulting mixture was stirred under ice-cooling for 30 minutes. Afterstirring, saturated aqueous ammonium chloride solution was added to thereaction mixture to quench the reaction, and then the reactiontemperature was raised to room temperature. After evaporation of thereaction mixture in vacuo, ethyl acetate and water were added to theresidue and then the resulting mixture was extracted with ethyl acetate.The extract was washed successively with water and saturated aqueoussodium chloride solution and dried over anhydrous sodium sulfate. Afterfiltration, the solvent was removed in vacuo, and the residue waspurified by chromatography on a silica gel column using a mixed solventof hexane and ethyl acetate (10:1) as the eluent to afford the titlecompound (19.32 g, yield: 98%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 7.45 (d, 1H, J=1.6 Hz), 7.33 (d,1H, J=1.5 Hz), 6.41 (dd, 1H, J=2.9 Hz, 1.6 Hz), 6.36–6.35 (m, total 2H),6.33 (d, 1H, J.=15.9 Hz), 6.26–6.22 (m, total 2H), 6.20 (d, 1H, J=15.9Hz), 5.59 (d, 1H, J=12.7 Hz), 5.22 (br s, 1H), 4.82 (br s, 1H), 4.43 (d,1H, J=11.0 Hz), 4.32 (d, 1H, J=11.0 Hz), 4.25 (d, 1H, J=11.0 Hz), 4.18(d, 1H, J=11.0 Hz), 2.36–2.32 (m, total 4H), 1.67–1.22 (m, total 40H),0.92–0.87 (s, total 6H).

IR spectrum ν_(max) cm⁻¹ (Liquid Film): 3445, 2962, 2933, 2873, 2250,1720, 1497, 1457, 1391, 1368, 1249, 1165, 1075, 1015.

Mass spectrum (FAB⁺) m/z: 388((M+Na)⁺), 366((M+H)⁺).

Reference Example 3(4R)-4-Methyl-4-[2-(furan-2-yl)ethenyl]-1,3-oxazolidin-2-one

To a solution of(2R)-2-t-butoxycarbonylamino-1-n-hexanoyloxy-2-methyl-4-(furan-2-yl)-3-butene(19.32 g, 52.9 mmol) obtained in Reference example (2c) in a mixedsolvent of tetrahydrofuran (53 ml) and methanol (53 ml) was added 2Naqueous sodium hydroxide solution (53 ml), and the resulting mixture wasstirred at room temperature for 1 hour. After stirring, water anddichloromethane were added to the reaction mixture, and the resultingmixture was extracted with dichloromethane. The extract was washed withsaturated aqueous sodium chloride solution and dried over anhydroussodium sulfate. After filtration, the solvent was removed in vacuo toafford the crude product(14.84 g, yield: 100%).

Subsequently, to a solution of the crude product in tetrahydrofuran (150ml) was added a solution of potassium t-butoxide (7.20 g, 64.2 mmol) intetrahydrofuran (50 ml) with stirring under ice-cooling over a 10-minuteinterval, and the resulting mixture was stirred at the same temperaturefor 1 hour. After stirring, the reaction mixture was neutralized withacetic acid (3.65 ml, 63.8 mmol) and evaporated in vacuo. Water andethyl acetate were added to the residue obtained, and the resultingmixture was extracted with ethyl acetate. The extract was washed withsaturated aqueous sodium chloride solution and dried over anhydroussodium sulfate. After filtration, the solvent was removed in vacuo, andthe residue was purified by chromatography on a silica gel column usinga mixed solvent of hexane and ethyl acetate (1:1) as the eluent toafford the title compound (10.04 g, yield: 98%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 7.49 (d, 1H, J=1.6 Hz), 7.36 (d,1H, J=1.6 Hz), 6.46 (d, 1H, J=2.1 Hz), 6.43 (d, 1H, J=16.1 Hz),6.04–6.37 (m, total 2H), 6.30 (br s, 1H), 6.30 (d, 1H, J=3.3 Hz), 6.21(d, 1H, J=12.7 Hz), 6.18 (d, 1H, J=16.1 Hz), 5.88 (br s, 1H), 5.62 (d,1H, J=12.7 Hz), 4.41 (d, 1H, J=8.5 Hz), 4.37 (d, 1H, J=8.5 Hz), 4.23 (d,1H, J=8.3 Hz), 4.17 (d, 1H, J=8.3 Hz), 1.65 (s, 3H), 1.54 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (CDCl₃): 3451, 2252, 1757, 1396, 1374, 1281,1165, 1044, 1016.

Mass spectrum (EI⁺) m/z: 193(M⁺), 178(base), 163, 148, 135, 120, 107,91, 81, 65.

Reference Example 4(4R)-4-Methyl-4-[2-(furan-2-yl)ethyl]-1,3-oxazolidin-2-one

To a suspension of 10% palladium-charcoal (50% wet with water) (1.00 g)in methanol (20 ml) was added a solution of(4R)-4-methyl-4-[2-(furan-2-yl)ethenyl]-1,3-oxazolidin-2-one (10.04 g,52.0 mmol) obtained in Reference example 3 in methanol (180 ml) withstirring, and the resulting mixture was stirred at room temperatureunder a hydrogen atmosphere for 40 minutes. After stirring, thepalladium-charcoal in the reaction mixture was filtered off usingcelite, and the filtrate was evaporated in vacuo. The residue obtainedwas purified by chromatography on a silica gel column using a mixedsolvent of hexane and ethyl acetate (3:2–1:1) as the eluent to affordthe title compound (7.95 g, yield: 78%).

Furthermore, the(4R)-4-methyl-4-[2-(furan-2-yl)ethyl]-1,3-oxazolidin-2-one obtained wasanalyzed with a HPLC column for separating optical isomers [ChiralPak AD(0.46 cm×25 cm), Daicel Chemical Industries, Ltd., mobile phase:n-hexane/2-propanol (85/15), flow rate: 1.0 ml/min], and its opticalpurity was determined.

From the results of the HPLC analysis, it was confirmed that thecompound eluted first (retention time: 13.09 min) was the 4S-isomer, andthe compound eluted afterward (retention time: 15.43 min) was the4R-isomer, and that the optical purity of the product synthesized was84% ee.

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 7.31 (br s, 1H,), 6.29 (br d, 1H,J=2.6 Hz), 6.03 (d, 1H, J=2.6 Hz), 5.92 (br s, 1H), 4.11 (d, 1H, J=8.4Hz), 4.04 (d, 1H, J=8.4 Hz), 2.72 (t, 2H, J=8.0 Hz), 1.98–1.94 (m, 2H),1.68–1.61 (m, 2H), 1.38 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (CDCl₃): 3450, 2975, 2928, 2250, 1755, 1599,1508, 1400, 1381, 1147, 1045, 1010.

Mass spectrum (EI⁺) m/z: 195(M⁺), 178, 164, 134, 121, 100(base), 96, 94,81, 56.

Reference Example 5(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-(furan-2-yl)butane (5a)(2R)-2-Amino-2-methyl-4-(furan-2-yl)butan-1-ol ½ D-(−)tartrate

To a solution of(4R)-4-methyl-4-[2-(furan-2-yl)ethyl]-1,3-oxazolidin-2-one (29.9 g,153.2 mmol) obtained in Reference example 4 in a mixed solvent oftetrahydrofuran (150 ml) and methanol (150 ml) was added 5N aqueouspotassium hydroxide solution (150 ml) with stirring, and the resultingmixture was refluxed for 3 days. After cooling, water was added to thereaction mixture, and the resulting mixture was extracted withdichloromethane. The extract was dried over anhydrous sodium sulfate.After filtration, the filtrate was evaporated in vacuo.

Subsequently, to a solution of the residue obtained in ethanol (250 ml)was added a solution of D-(−)-tartaric acid (11.5 g, 76.6 mmol) inethanol (100 ml) with stirring, and the resulting mixture was stirredfor 10 minutes. The crude crystals precipitated were collected byfiltration and then recrystallized from a mixed solvent of ethanol (300ml) and water (75 ml) to afford the title compound (24.4 g, yield: 65%)as colorless plate crystals.

Subsequently, to a suspension of(2R)-2-amino-2-methyl-4-(furan-2-yl)butan-1-ol ½ D-(−)tartrate (51.2 mg,0.16 mmol) obtained above in dichloromethane (1.6 ml) were addedsuccessively di-t-butyl dicarbonate (0.17 g, 0.78 mmol), triethylamine(0.22 ml, 1.58 mmol) and 4-dimethylaminopyridine (3.0 mg, 0.025 mmol)with stirring, and the resulting mixture was stirred at room temperaturefor 20 minutes. After stirring, water was added to the reaction mixture,and the resulting mixture was evaporated in vacuo. The residue obtainedwas purified by chromatography on a silica gel column using a mixedsolvent of hexane and ethyl acetate (1:1) as the eluent to afford(4R)-4-methyl-4-[2-(furan-2-yl)ethyl]-1,3-oxazolidin-2-one (18.0 mg,yield: 58%).

Furthermore, the(4R)-4-methyl-4-[2-(furan-2-yl)ethyl]1,3-oxazolidin-2-one obtained abovewas analyzed with a HPLC column for separating optical isomers[ChiralPak AD (0.46 cm×25 cm), Daicel Chemical Industries, Ltd., mobilephase: n-hexane/2-propanol (85/15), flow rate: 1.0 ml/min] in a similarmanner to that mentioned in Reference example 4, and its optical puritywas determined.

From the results of the HPLC analysis, it was confirmed that thecompound eluted first (retention time: 13.09 min) was the 4S-isomer, andthe compound eluted afterward (retention time: 15.43 min) was the4R-isomer, and that the optical purity of this product was 99.3% ee.

According to the results obtained above, the optical purity of the(2R)-2-amino-2-methyl-4-(furan-2-yl)butan-1-ol ½ D-(−)tartratesynthesized was confirmed to be more than 99.3%.

Melting point : 225° C.,

Angle of rotation : [α]_(D)=−13.43 (c=1.00, MeOH),

¹H-NMR spectrum (CD₃OD, 400 MHz) δ : 7.36 (d, 1H, J=2.0 Hz), 6.30 (dd,1H, J 2.8 Hz, 2.0 Hz), 6.09 (d, 1H, J=2.8 Hz), 3.58 (d, 1H, J=11.6 Hz),3.51 (d, 1H, J=11.6 Hz), 2.77–2.68 (m, 2H), 2.07–1.88 (m, 2H), 1.28 (s,3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3405, 3226, 3135, 2943, 2597, 1598,1528, 1401, 1299, 1228, 1124, 1079, 1003, 740.

Mass spectrum (FAB⁺) m/z: 170((M+H)⁺; as the free form of the titlecompound),

Elemental analysis (% as C₉H₁₅NO₂.½C₄H₆O₆) Calculated: C; 54.09; H,7.43, N, 5.73; Found: C; 53.93; H, 7.30, N, 5.79.

(5b) (2R)-1-Acetoxy-2-acetylamino-2-methyl-4-(furan-2-yl)butane

To a suspension of (2R)-2-amino-2-methyl-4-(furan-2-yl)butan-1-ol ½D-(−)tartrate (24.21 g, 99.1 mmol) obtained in Reference example (5a) ina mixed solvent of dichloromethane (400 ml) and water (100 ml) was addedan aqueous sodium hydroxide solution [prepared by dissolving sodiumhydroxide (97% pure) (22.34 g) in water (100 ml)] with stirring, and theresulting mixture was stirred at room temperature for 20 minutes. Afterstirring, the reaction mixture was extracted with dichloromethane, andthe extract was dried over anhydrous sodium sulfate. After filtration,the solvent was evaporated in vacuo.

Subsequently, to a solution of the residue obtained in dichloromethane(500 ml) were added successively triethylamine (138 ml, 993 mmol),acetic anhydride (46.5 ml, 493 mmol) and 4-dimethylaminopyridine (1.21g, 9.9 mmol), and the resulting mixture was stirred at room temperaturefor 1 hour. After stirring, methanol was added to the reaction mixtureto quench the reaction, and the reaction mixture was evaporated invacuo. Ethyl acetate and water were added to the residue obtained, andthe resulting mixture was extracted with ethyl acetate. The extract waswashed successively with water and saturated aqueous sodium chloridesolution and dried over anhydrous sodium sulfate. After filtration, thesolvent was removed in vacuo, and the residue was purified bychromatography on a silica gel column using a mixed solvent of ethylacetate and hexane (2:1) as the eluent to afford the title compound(25.11 g, yield: 100%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 7.30(d, 1H, J=1.8 Hz), 6.28. (dd,1H, J=3.0 Hz, 1.8 Hz), 6.01 (d, 1H., J=3.0 Hz), 5.36 (br s, 1H), 4.30(d, 1H, J.=11.1 Hz), 4.17 (d, 1H, J=11.1 Hz), 2.66 (t, 2H, J=8.3 Hz),2.30–2.22 (m, 1H), 2.09 (s, 3H), 2.02–1.94 (m, 1H), 1.92 (s, 3H), 1.35(s, 3H).

Mass spectrum (EI⁺) m/z: 253(M⁺), 211, 194, 180, 138, 134(base), 121,99, 94, 81, 74, 57, 43.

Reference Example 6(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-(5-bromofuran-2-yl)butane

To a solution of(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(furan-2-yl)butane (5.85 g, 23.1mmol) obtained in Reference example (5b) in N,N-dimethylformamide (10.0ml) were added several small portions of N-bromosuccinimide (4.32 g,24.3 mmol) with stirring under ice-cooling, and the resulting mixturewas stirred at the same temperature for 30minutes. After stirring, tothe reaction mixture were added successively 10% aqueous sodiumthiosulfate solution and saturated aqueous sodium hydrogencarbonatesolution, and the resulting mixture was extracted with ether. Theextract was washed with saturated aqueous sodium chloride solution anddried over anhydrous sodium sulfate. After filtration, the solvent wasremoved in vacuo, and the residue was purified by chromatography on asilica gel column using a mixed solvent of ethyl acetate and hexane(2:1) as the eluent to afford the crude product. The crude productobtained was furthermore purified using a preparative reversed phaseHPLC column [TSK-GEL ODS-80Ts (5.0 cm×30 cm), TOSO, mobile phase:acetonitrile/water (50:50), flow rate: 40 ml/min] to afford the titlecompound (2.95 g, yield: 38%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 6.18 (d, 1H, J=3.3 Hz), 5.99 (d,1H, J=3.3 Hz), 5.37 (br s, 1H), 4.29 (d, 1H, J=11.3 Hz), 4.16 (d, 1H,J=11.3 Hz), 2.70–2.57 (m, 2H), 2.30–2.22 (m, 1H), 2.10 (8, 3H),2.01–1.93 (m, 1H), 1.94 (s, 3H), 1.34 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (Liquid Film): 3300, 3074, 2978, 2938, 1742,1658, 1549, 1510, 1450, 1373, 1241, 1128, 1012, 945, 922, 784, 733, 605.

Mass spectrum (FAB⁺) m/z: 332((M+H)⁺).

Reference Example 7(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-(5-iodofuran-2-yl)butane

To a solution of(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(furan-2-yl)butane (5.11 g, 19.8mmol) obtained in Reference example (5b) in chloroform (100 ml) wereadded successively pyridine (8.0 ml, 99.1 mmol) and iodine (10.07 g,39.7 mmol), and the resulting mixture was stirred at 60° C. for 3 hours.After cooling, 10% aqueous sodium thiosulfate solution was added to thereaction mixture to quench the reaction, and the reaction mixture wasextracted with dichloromethane. The extract was washed successively withwater, saturated aqueous sodium hydrogencarbonate solution and saturatedaqueous sodium chloride solution and dried over anhydrous sodiumsulfate. After filtration, the solvent was removed in vacuo, and theresidue was purified by chromatography on a silica gel column using amixed solvent of ethyl acetate and hexane (3:2) as the eluent to affordthe crude product (5.57 g). The crude product obtained was furthermorepurified using a preparative reversed phase HPLC column [TSK-GEL ODS-80Ts (5.0 cm×30 cm), TOSO, mobile phase: acetonitrile/water (50:50), flowrate: 40 ml/min] to afford the title compound (2.9467 g, yield: 39%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 6.42 (d, 1H, J=3.1 Hz), 5.95 (d,1H, J=3.1 Hz), 5.37 (br s, 1H), 4.29 (d, 1H, J=11.1 Hz), 4.16 (d, 1H,J=11.1 Hz), 2.72–2.63 (m, 2H), 2.29–2.21 (m, 1H), 2.10 (s, 3H),2.05–1.93 (m, 1H), 1.94 (s, 3H), 1.34 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (CHCl₃): 3444, 2941, 1736, 1681, 1598, 1512,1374, 1252, 1103, 1043, 1011, 947, 912.

Mass spectrum (FAB⁺) m/z: 380((M+H)⁺).

Reference Example 8 (1-Methylpyrrol-2-yl)methyl triphenylphosphoniumiodide

A mixture of 35% aqueous formaldehyde solution (20.8 ml, 264.3 mmol) anddimethylamine hydrochloride (22.70 g, 278.4 mmol) was added to1-methylpyrrole (21.42 g, 264.1 mmol) with stirring under ice-coolingover a 90-minute interval, and then the resulting mixture was stirred atroom temperature for 6 hours. After stirring, 10% aqueous sodiumhydroxide solution (150 ml) was added to the reaction mixture, and thereaction mixture was extracted with ether. The extract was washed withsaturated aqueous sodium chloride solution and dried over anhydroussodium sulfate. After filtration, the solvent was removed in vacuo, andthe residue was purified by chromatography on a silica gel column usinga mixed solvent of dichloromethane and methanol (10:1) as the eluent toafford 2-(N,N-dimethylaminomethyl)-1-methylpyrrole (31.47 g, yield:86%).

Subsequently, to absolution of2-(N,N-dimethylaminomethyl)-1-methylpyrrole (30.00 g, 217.5 mmol)obtained above in ethanol (220 ml) was added methyl iodide (16.2 ml,260–2 mmol) with stirring under ice-cooling, and then the resultingmixture was stirred at room temperature for 2 hours. After stirring,ethyl acetate (220 ml) was added to the reaction mixture. The crystalsprecipitated were collected by filtration, washed with ethyl acetate anddried to afford (1-methylpyrrol-2-yl)methyl trimethylammonium iodide(55.34 g, yield: 91%).

Subsequently, to a suspension of (1-methylpyrrol-2-yl)methyltrimethylammonium iodide (55.34 g, 197.5 mmol) obtained above inacetonitrile (400 ml) was added triphenylphosphine (62.20 g, 237.1 mmol)with stirring, and the resulting mixture was stirred at 80° C. for 10hours. After cooling, the reaction mixture was concentrated to aboutone-half of its initial volume, to which was added ethyl acetate (200ml). The crystals precipitated were collected by filtration, washed withethyl acetate and dried in vacuo to afford the title compound (77.14 g,yield: 81%).

Reference Example 9(2R)-2-t-Butoxycarbonylamino-1-n-hexanoyloxy-2-methyl-4-(1-methylpyrrol-2-yl)-3-butene

The title compound was synthesized in a yield of 80% using(1-methylpyrrol-2-yl)methyl triphenylphosphonium iodide obtained inReference example 8 and(2S)-2-t-butoxycarbonylamino-3-n-hexanoyloxy-2-methyl-1-propanalobtained in Reference example (2b) as the starting materials byconducting the reaction similar to that mentioned in Reference example(2c).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 6.60 (t, 1H, J=2.3 Hz), 6.57 (t,1H, J=2.3 Hz), 6.38 (d, 1H, J=16.1 Hz), 6.30–6.26 (m, total 2H), 6.27(d, 1H, J=12.5 Hz), 6.11 (t, 1H, J=3.2 Hz), 6.08 (t, 1H, J=3.2 Hz), 5.99(d, 1H, J=16.1 Hz), 5.58 (d, 1H, J=12.5 Hz) 5.04 (br s, 1H), 4.81 (br s,1H), 4.34–4.16 (m, total 4H), 3.60 (s, 3H), 3.54 (s, 3H), 2.36–2.30 (m,total 4H), 1.67–1.22 (m, total 4H), 0.92–0.87 (s, total 6H).

Mass spectrum (EI⁺) m/z: 280(M⁺), 249, 224, 193(base), 164, 149, 132,108, 94, 57.

Reference Example 10(4R)-4-Methyl-4-[2-(1-methylpyrrol-2-yl)ethenyl]-1,3-oxazolidin-2-one

The title compound was synthesized in a yield of 76% using(2R)-2-t-butoxycarbonylamino-1-n-hexanoyloxy-2-methyl-4-(1-methylpyrrol-2-yl)-3-buteneobtained in Reference example 9 as the starting material by conductingthe reaction similar to that mentioned in Reference example 3.

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 6.67 (t, 1H, J=2.1 Hz), 6.62 (t,1H, J=1.5 Hz), 6.48 (d, 1H, J=15.7 Hz), 6.36 (dd, 1H, J=3.7 Hz, 1.5 Hz),6.31 (d, 1H, J=12.2. Hz), 6.14–6.10 (m, total 2H), 6.07 (br d, 1H, J=3.6Hz), 5.99 (d, 1H, J=15.7 Hz), 5.65 (d, 1H, J=12.2 Hz) 5.46 (br s, 1H),5.11 (br s, 1H), 4.31 (d, 1H, J=8.2 Hz), 4.22 (d, 1H, J=8.2 Hz), 4.17(d, 1H, J=8.2 Hz), 4.16 (d, 1H, J=8.2 Hz), 3.62 (s, 3H), 3.55 (s, 3H),1.59 (s, 3H), 1.57 (s, 3H).

Mass spectrum (EI⁺) m/z: 206(M⁺, base), 191, 176, 161, 147, 132, 120,106, 94, 81, 77.

Reference Example 11(4R)-4-Methyl-4-[2-(1-methylpyrrol-2-yl)ethyl]-1,3-oxazolidin-2-one

The title compound was synthesized in a yield of 78% using(4R)-4-methyl-4-[2-(1-methylpyrrol-2-yl)ethenyl.]-1,3-oxazolidin-2-oneobtained in Reference example 10 as the starting material by conductingthe reaction similar to that mentioned in Reference example 4.

Furthermore, the(4R)-4-methyl-4-[2-(1-methylpyrrol-2-yl)ethyl]-1,3-oxazolidin-2-oneobtained above was analyzed with a HPLC column for separating opticalisomers [ChiralCel OJ (0.46 cm×25 cm), Daicel Chemical Industries, Ltd.,mobile phase: n-hexane/2-propanol (70/30), flow rate: 1.0 ml/min], andits optical purity was determined.

From the results of the HPLC analysis, it was confirmed that thecompound eluted first (retention time: 12.29 min) was the 4S-isomer, andthe compound eluted afterward (retention time: 15.39 min) was the4R-isomer, and that the optical purity of the product synthesized was75% ee.

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 6.58 (t, 1H, J 2.4 Hz), 6.05 (dd,1H, J=3.2 Hz, 2.4. Hz), 5.88 (br d, 1H, J=3.2 Hz), 5.15 (br s, 1H), 4.14(d, 1H, J=8.3 Hz), 4.07 (d, 1H, J=8.3 Hz), 2.70–2.58 (m, 2H), 2.00–1.87(m, 2H), 1.42 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr): 3289, 3103, 2977, 2938, 1759, 1713,1495, 1397, 1381, 1309, 1281, 1231, 1032, 945, 928, 776, 718, 706, 656.

Mass spectrum (EI⁺) m/z: 208(M⁺), 108(base), 94, 81, 56, 42.

Reference Example 12(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-(1-methylpyrrol-2-yl)butane

To a solution of(4R)-4-methyl-4-[2-(1-methylpyrrol-2-yl)ethyl]-1,3-oxazolidin-2-one(1.53 g, 7.36 mmol) obtained in Reference example 11 in a mixed solventof tetrahydrofuran (30 ml) and methanol (15 ml) was added 5N aqueouspotassium hydroxide solution (15 ml, 75 mmol), and the resulting mixturewas refluxed for 5 days. After cooling, water was added to the reactionmixture, and the resulting mixture was extracted with dichloromethane.The extract was dried over anhydrous sodium sulfate. After filtration,the solvent was removed in vacuo, and the residue was purified bychromatography on a basic silica gel column (NH type) using a mixedsolvent of dichloromethane and methanol (100:1) as the eluent to affordthe crude product (1.32 g, yield: 98%).

Subsequently, to a solution of the crude product (1.32 g, 7.24 mmol)thus obtained in dichloromethane (36 ml) were added successivelytriethylamine (10.0 ml, 71.9 mmol), acetic anhydride (3.4 ml, 36.1 mmol)and 4-dimethylaminopyridine (88 mg, 0.72 mmol) with stirring, and theresulting mixture was stirred at room temperature for 40 minutes. Afterstirring, methanol(1.46 ml, 36.0 mmol) was added to the reaction mixtureto quench the reaction, and the reaction mixture was evaporated invacuo. Ethyl acetate and water were added to the residue obtained, andthe resulting mixture was extracted with ethyl acetate. The extract waswashed successively with water, saturated aqueous sodiumhydrogencarbonate solution and saturated aqueous sodium chloridesolution and dried over anhydrous sodium sulfate. After filtration, thefiltrate was concentrated to dryness in vacuo, and the residue waspurified by chromatography on a silica gel column using a mixed solventof ethyl acetate and hexane (3:2–1:0) as the eluent to afford the titlecompound (1.89 g, yield: 98%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 6.54(t, 1H, J=2.4 Hz), 6.04 (t, 1H,J=2.4 Hz), 5.88 (d, 1H, J=2.4 Hz), 5.39 (br s, 1H), 4.33 (d, 1H, J=11.2Hz), 4.20 (d, 1H, J=11.2 Hz), 2.60–2.51 (m, 2H), 2.26–2.19 (m, 1H), 2.09(s., 3H), 1.97–1.89 (m, 4H), 1.38 (s, 3H).

Mass spectrum (FAB⁺) m/z: 267((M⁺H)⁺), 266(M⁺).

Reference Example 13(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-(1-methyl-5-iodopyrrol-2-yl)butane

To a solution of(2R)-1-acetoxy-2-acetylamino-2-methyl-4-(1-methylpyrrol-2-yl)butane(1.89 g, 7.10 mmol) obtained in Reference example 12 in chloroform (35ml) were added successively pyridine (2.9 ml, 35.9 mmol) and iodine(3.60 g, 14.17 mmol) with stirring under ice-cooling, and the resultingmixture was stirred at the same temperature for 10 minutes. Afterstirring, 10% aqueous sodium thiosulfate solution was added to thereaction mixture to quench the reaction, and the reaction mixture wasconcentrated to about one-half of its initial volume, and extracted withethyl acetate. The extract was washed successively with saturatedaqueous sodium hydrogencarbonate solution and saturated aqueous sodiumchloride solution and dried over anhydrous sodium sulfate. Afterfiltration, the filtrate was concentrated to dryness in vacuo, and theresidue obtained was purified by chromatography on a silica gel columnusing a mixed solvent of ethyl acetate and hexane (3:2) as the eluent toafford the title compound (1.40 g, yield: 50%)

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 6.28 (d, 1H, J=3.6 Hz), 5.94 (d,1H, J=3.6 Hz), 5.36 (br s., 1H), 4.32 (d, 1H, J=11.0 Hz), 4.17 (d, 1H,J=11.0 Hz), 3.49 (s, 3H), 2.67–2.59 (m, 2H), 2.27–2.19 (m, 1H), 2.09 (s,3H), 1.96–1.87 (m, 4H), 1.36 (s, 3H).

Mass spectrum (FAB⁺) m/z: 393((M+H)⁺), 392(M⁺).

Reference Example 14(2R)-2-t-Butoxycarbonylamino-2-ethyl-1-n-hexanoyloxy-4-(furan-2-yl)-3-butene(14a) (2R)-2-t-Butoxycarbonylamino-2-ethyl-3-n-hexanoyloxy-1-propanol.

To a suspension of 2-t-butoxycarbonylamino-2-ethylpropane-1,3-diol (52.9g, 241 mmol) in isopropyl ether (1.0 1) were added successively vinylhexanoate (41 ml, 254 mmol) and lipase [Immobilized lipase fromPseudomonas sp., TOYOBO, 0.67 U/mg] (2.1 g) with stirring, and theresulting mixture was stirred at room temperature for 4 hours. Afterstirring, the reaction mixture was filtered and evaporated in vacuo, andthe residue was purified by chromatography on a silica gel column usinga mixed solvent of hexane and ethyl acetate (7:1–4:1–2:1) as the eluentto afford the title compound (66.8 g, yield: 87%)

Furthermore, the(2R)-2-t-butoxycarbonylamino-2-ethyl-3-n-hexanoyloxy-1-propanol obtainedabove was analyzed with a HPLC column for separating optical isomers[ChiralCel OF (0.46 cm×25 cm), Daicel Chemical Industries, Ltd., mobilephase: hexane/2-propanol (80/20), flow rate: 0.5 ml/min], and itsoptical purity was determined.

From the results of the HPLC analysis, it was confirmed that thecompound eluted first (retention time: 7.35 min) was the 2S-isomer, andthe compound eluted afterward (retention time: 7.86 min) was the2R-isomer, and that the optical purity of the product synthesized was93% ee.

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 4.76 (br s, 1H), 4.24 (d, 1H,J=11.0 Hz), 4.10 (d, 1H, J=11.0 Hz), 3.65–3.62 (m, 2H), 2.35 (t, 2H,J=7.7 Hz), 1.78–1.69 (m, 1H.), 1.63–1.53 (m, 4H), 1.44 (s, 9H),1.30–1.25 (m, 4H), 0.87–0.83 (m, 6H).

Mass spectrum (FAB⁺) m/z: 340((M+Na)⁺), 318((M+H)⁺).

(14b) (2S)-2-t-Butoxycarbonylamino-2-ethyl-3-n-hexanoyloxy-1-propanal

To a solution of(2R)-2-t-butoxycarbonylamino-3-n-hexanoyloxy-2-ethyl-1-propanol (66.7 g,210 mmol) obtained in Reference example (14a) in dichloromethane (700ml) were added successively molecular sieves 4A (117 g) and pyridiniumdichromate (117 g, 311 mmol) with stirring under ice-cooling, and thenthe resulting mixture was stirred at room temperature for 2 hours. Afterstirring, ether was added to the reaction mixture, and the resultingmixture was filtered. The filtrate was evaporated in vacuo, and theresidue was purified by chromatography on a silica gel column using amixed solvent of hexane and ethyl acetate (10:1–5:1) as the eluent toafford the title compound (45.9 g, yield: 69%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 9.34, (s, 1H), 5.30 (br s, 1H),4.60 (d, 1H, J=11.4 Hz), 4.40 (d, 1H, J=11.4 Hz), 2.28 (t, 2H, J=7.3Hz), 2.18–2.06 (m, 1H), 1.79–1.69 (m, 1H), 1.62–1.55 (m, 2H), 1.44 (s,9H), 1.34–1.22 (m, 4H), 0.90 (t, 3H, J=7.3 Hz), 0.81 (t, 3H, J=7.3 Hz).

Mass spectrum (FAB⁺) m/z: 338((M+Na)⁺), 316((M+H)⁺).

(14c)(2R)-2-t-Butoxycarbonylamino-2-ethyl-1-n-hexanoyloxy-4-(furan-2-yl)-3-butene

To a suspension of (furan-2-yl)methyl triphenylphosphonium bromide (4.04g, 9.54 mmol) obtained in Reference example 1 in tetrahydrofuran (32.4ml) was added potassium t-butoxide (1.06 g, 9.45 mmol) with stirringunder ice-cooling, and the resulting mixture was furthermore stirredunder ice-cooling for 15 minutes. After stirring, to the reactionmixture was added a solution of(2S)-2-t-butoxycarbonylamino-2-ethyl-3-n-hexanoyloxy-1-propanal (2.01 g,6.37 mmol) obtained in Reference example (14b) in tetrahydrofuran (10ml) with stirring under ice-cooling over a 5-minute interval, and theresulting mixture was furthermore stirred under ice-cooling for 30minutes. After stirring, saturated aqueous ammonium chloride solutionwas added to the reaction mixture to quench the reaction, and thereaction temperature was raised to room temperature. After evaporationof the reaction mixture in vacuo, ethyl acetate and water were added tothe residue, and the resulting mixture was extracted with ethyl acetate.The extract was washed with saturated aqueous sodium chloride solutionand dried over anhydrous sodium sulfate. After filtration, the solventwas removed in vacuo, and the residue was purified by chromatography ona silica gel column using a mixed solvent of hexane and ethyl acetate(5:1) as the eluent to afford the title compound (2.385 g, yield: 99%)

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 7.44 (br d, 1H, J=.1.5 Hz), 7.33(br d, 1H, J=1.5 Hz), 6.41 (dd, 1H, J=2.9 Hz, 1.5 Hz), 6.38 (d, 1H,J=2.9 Hz), 6.36 (dd, 1H, J=2.9 Hz, 1.5 Hz), 6.29 (d, 1H, J=16.8 Hz),6.28 (d, 1H, J=12.5 Hz), 6.,22 (d, 1H, J=2.9 Hz), 6.09 (d, 1H, J=16.8Hz), 5.47 (d, 1H, J=12.5 Hz), 5.21 (br s, 1H), 4.66 (br s, 1H), 4.50 (d,1H, J=11.7 Hz), 4.41 (d, 1H, J 11.7 Hz), 4.33 (br s, 2H), 2.31 (q, total4H, J=7.7 Hz), 2.08–1.88 (m, total 4H),, 1.47–1.42 (m, total 10H),1.32–1.26 (m, total 18H), 0.93–0.86 (m, total 12H).

IR spectrum ν_(max) cm⁻¹ (CHCl₃): 3446, 2970, 2933, 2873, 1722, 1494,1459, 1391, 1380, 1368, 1249, 1163.

Mass spectrum (FAB⁺) m/z: 402((M+Na)⁺), 379(M⁺).

Reference Example 15(4R)-4-Ethyl-4-[2-(furan-2-yl)ethenyl]-1,3-oxazolidin-2-one

To a solution of(2R)-2-t-butoxycarbonylamino-2-ethyl-1-n-hexanoyloxy-4-(furan-2-yl)-3-butene(2.33 g, 6.14 mmol) obtained in Reference example 14 in a mixed solventof tetrahydrofuran (7 ml) and methanol (7 ml) was added 1.8N aqueoussodium hydroxide solution (7 ml), and the resulting mixture was stirredat room temperature for 3 hours. After stirring, water and ethyl acetatewere added to the reaction mixture, and the resulting mixture wasextracted with ethyl acetate. The extract was washed with saturatedaqueous sodium chloride solution and dried over anhydrous sodiumsulfate. After filtration, the solvent was removed in vacuo to affordthe crude product (1.68 g, yield: 97%).

Subsequently, to a solution of the crude product obtained above intetrahydrofuran (30 ml) was added potassium t-butoxide (1.21 g, 10.8mmol) with stirring, and the resulting mixture was stirred at the sametemperature for 3hours. After stirring, water and ethyl acetate wereadded to the reaction mixture, and the resulting mixture was extractedwith ethyl acetate. The extract was washed with saturated aqueous sodiumchloride solution and dried over anhydrous sodium sulfate. Afterfiltration, the solvent was removed in vacuo, and the residue waspurified by chromatography on a silica gel column using a mixed solventof hexane and ethyl acetate (3:1–1:1) as the eluent to afford the titlecompound (1.24 g, quantitative yield).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 7.43 (d, 1H, J=1.5 Hz), 7.32 (d,1H, J=1.5 Hz), 6.45 (dd, 1H, J 3.7 Hz, 1.5 Hz), 6.44 (d, 1H, J=16.1 Hz),6.39 (dd, 1H, J=3.7 Hz, 1.5 Hz), 6.37 (d, 1H, J=3.7 Hz), 6.29 (d, 1H,J=3.7 Hz), 6.25 (d, 1H, J=12.5 Hz), 6.13 (d, 1H, J=16.1 Hz), 5.62 (br s,total 2H), 5.53 (d, 1H, J=12.5 Hz), 4.44 (d, 1H, J;=8.8 Hz), 4.36 (d,1H, J=8.8 Hz), 4.24 (d, 1H, J=8.8 Hz), 4.22 (d, 1H, J=8.8 Hz), 1.93 (q,2H, J=7.3 Hz), 1.85–1.76 (m, 2H), 0.99 (t, 3H, J=7.3 Hz), 0.98 (t, 1H,J=7.3 Hz).

IR spectrum ν_(max) cm⁻¹ (CDCl₃): 3453, 2975, 1757, 1396, 1373, 1053,1015.

Mass spectrum (EI⁺) m/z: 207(M⁺), 178(base), 135, 107.

Reference Example 16(4R)-4-Ethyl-4-[2-(furan-2-yl)ethyl]-1,3-oxazolidin-2-one

To a solution of(4R)-4-ethyl-4-[2-(furan-2-yl)ethenyl]-1,3-oxazolidin-2-one (1.24 g,5.99 mmol) obtained in Reference example 15 in methanol (40 ml) wasadded 10% palladium-charcoal (50% wet with water) (124 mg), and theresulting mixture was stirred at room temperature under a hydrogenatmosphere for 2 hours. After stirring, the internal atmosphere wasreplaced with nitrogen, and the palladium-charcoal, in the reactionmixture was filtered off using celite, which was washed with ethylacetate. The filtrate and the washings were combined and concentrated todryness in vacuo, and the residue was purified by chromatography on asilica gel column using a mixed solvent of hexane and ethyl acetate(1:1–1:2) as the eluent to afford the title compound (144.4 mg, yield:12%).

¹H-NMR spectrum (CDCl₃, 400 MHz.) δ : 7.32 (br d, 1H, J=2.2 Hz), 6.29(t, 1H, J=2.2 Hz), 6.03 (br d, 1H, J=2.2 Hz), 5.40 (m, 1H), 4.11 (d, 1H,J=8.8 Hz), 4.07 (d, 1H, J=8.8 Hz), 2.74–2.67 (m, 2H), 1.97–1.93 (m, 2H),1.72–1.64 (m, 2H), 0.96 (t, 3H, J=7.3 Hz).

IR spectrum ν_(max) cm⁻¹ (CDCl₃): 3453, 2973, 229, 1757, 1601, 1397,1380, 1052.

Mass spectrum (EI⁺) m/z: 209(M⁺), 178., 114, 81(base).

Reference Example 17(2R)-1-Acetoxy-2-acetylamino-2-ethyl-4-(furan-2-yl)butane

To a solution of(4R)-4-ethyl-4-[2-(furan-2-yl)ethyl]-1,3-oxazolidin-2-one obtained inReference example-16 in a mixed solvent of tetrahydrofuran (2 ml),methanol (2 ml) and water (2 ml) was added potassium hydroxide (310 mg),and the resulting mixture was refluxed for 3 days. After cooling, waterwas added to the reaction mixture, and the resulting mixture wasextracted with dichloromethane. The extract was dried over anhydroussodium sulfate. After filtration, the solvent was removed in vacuo, andthe residue was purified by chromatography on a silica gel column usinga mixed solvent of dichloromethane and methanol (1:0–50:1) as the eluentto afford (2R)-2-amino-2-ethyl-4-(furan-2-yl)butan-1-ol (104.9 mg,yield: 83%).

Subsequently, to a solution of(2R)-2-amino-2-ethyl-4-(furan-2-yl)butan-1-ol obtained above indichloromethane (2.0 ml) were added successively triethylamine (0.64 ml,4.59 mmol), acetic anhydride (0.32 ml, 3.39 mmol) and4-dimethylaminopyridine (28 mg, 0.23 mmol), and the resulting mixturewas stirred at room temperature for 2.5 hours. After stirring, methanolwas added to the reaction mixture to quench the reaction, and thereaction mixture was evaporated in vacuo. Ethyl acetate and water wereadded to the residue obtained, and the resulting mixture was extractedwith ethyl acetate. The extract was washed successively with water andsaturated aqueous sodium chloride solution and dried over anhydroussodium sulfate. After filtration, the solvent was removed in vacuo, andthe residue was purified by chromatography on a silica gel column usinga mixed solvent of hexane and ethyl acetate (1:4) as the eluent toafford the title compound (146.5 mg, yield: 96%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 7.29 (d, 1H, J=2.2 Hz), 6.28 (dd,1H, J=2.9 Hz, 2.2 Hz), 6.00 (d, 1H, J=2.9 Hz), 5.24 (br s, 1H), 4.30 (d,1H, J=11.7 Hz), 4.28 (d, 1H, J=11.7 Hz), 2.62 (t, 2H, J=8.1 Hz),2.21–2.13 (m, 1H), 2.08 (s, 3H), 2.08–1.99 (m, 1H), 1.94 (s, 3H),1.86–1.72 (m, 2H), 0.87 (t, 3H, J=7.3 Hz).

IR spectrum ν_(max) cm⁻¹ (CDCl₃): 3442, 2975, 1739, 1680, 1600, 1510,1462, 1383, 1368, 1248, 1043.

Mass spectrum (FAB⁺) m/z: 290((M+Na)⁺), 268((M+H)⁺).

Reference Example 18(2R)-1-Acetoxy-2-acetylamino-2-ethyl-4-(5-iodofuran-2-yl)butane

To a solution of(2R)-1-acetoxy-2-acetylamino-2-ethyl-4-(furan-2-yl)butane obtained inReference example 17 in chloroform (5.4 ml) were added successivelypyridine (0.22 ml, 2.73 mmol) and iodine (278 mg, 1.10 mmol), and theresulting mixture was stirred at 60° C. for 8 hours. After cooling, 10%aqueous sodium thiosulfate solution was added to the reaction mixture toquench the reaction, and the reaction mixture was extracted with ethylacetate. The extract was washed successively with saturated aqueoussodium hydrogencarbonate solution and saturated aqueous sodium chloridesolution and dried over anhydrous sodium sulfate. After filtration, thesolvent was removed in vacuo, and the residue was purified bychromatography on a silica gel column using a mixed solvent of hexaneand ethyl acetate (1:4–1:6) as the eluent to afford the crude product(151 mg). The crude product obtained was furthermore purified using apreparative reversed phase HPLC column [TSK-GEL ODS-80 Ts (2.0 cm×25cm), TOSO, mobile phase: acetonitrile/water (60:40)] to afford the titlecompound (74.0 mg, yield: 35%)

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 6.42 (d, 1H, J=3.7 Hz), 5.95 (d,1H, J=3.7 Hz), 5.23 (m, 1H), 4.27 (s, 2H), 2.64 (t, 2H, J=8.4 Hz),2.18–2.12 (m, 1H), 2.09 (s, 3H), 2.05–1.97 (m, 1H), 1.95 (s, 3H),1.81–1.76 (m, 2H), 0.87 (t, 3H, J=7.3 Hz).

IR spectrum ν_(max) cm⁻¹ (CDCl₃): 3442, 2976, 1740, 1681, 1598, 1511,1462, 1383, 1368, 1246, 1105, 1043.

Mass spectrum (FAB⁺) m/z: 416((M+Na)⁺), 394((M+H)⁺)

Reference Example 19(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-(1-methylpyrrol-2-yl)butane(19a) (2R)-2-Amino-2-methyl-4-(1-methylpyrrol-2-yl)butan-1-ol ½D-(−)tartrate

To a solution of(4R)-4-methyl-4-[2-(1-methylpyrrol-2-yl)ethyl]-1,3-oxazolidin-2-one(17.92 g, 86.0 mmol) obtained in Reference example 11 in a mixed solventof tetrahydrofuran (250 ml) and methanol (125 ml) was added 5N aqueouspotassium hydroxide solution (125 ml), and the resulting mixture wasrefluxed for 4 days. After cooling, water was added to the reactionmixture, and the resulting mixture was extracted with dichloromethane.The extract was dried over anhydrous sodium sulfate. After filtration,the solvent was removed in vacuo.

Subsequently, to a solution of the residue obtained in ethanol (260 ml)was added D-(−)-tartaric acid (6.45 g, 43.0 mmol), and the resultingmixture was stirred for 2 hours. The crystals precipitated werecollected by filtration to afford the crude product (20.67 g). The crudeproduct (18.65 g) was recrystallized repeatedly three times, firstlyfrom a mixture of ethanol (370 ml) and water (37 ml), secondly from amixture of ethanol (300 ml) and water (30 ml), and finally from amixture of ethanol (240 ml) and water (24 ml), to afford the titlecompound (10.50 g, yield: 53%) as colorless flake crystals.

Subsequently, to a suspension of(2R)-2-amino-2-methyl-4-(1-methylpyrrol-2-yl)butan-1-ol ½ D-(−)tartrate(41.4 mg, 0.16 mmol) obtained above in dichloromethane (1.6 ml) wasadded successively di-t-butyl dicarbonate (0.1758 g, 0.81 mmol),triethylamine (0.225 ml, 1.62 mmol) and 4-dimethylaminopyridine (2.0 mg,0.016 mmol) with stirring, and the resulting mixture was stirred at roomtemperature for 30 minutes. After stirring, water was added to thereaction mixture, and the resulting mixture was evaporated in vacuo. Theresidue obtained was purified by chromatography on a silica gel columnusing a mixed solvent of hexane and ethyl acetate (3:2–2:1) as theeluent to afford(4R)-4-methyl-4-[2-(1-methylpyrrol-2-yl)ethyl]-1,3-oxazolidin-2-one(17.7 mg, yield: 53%)

Furthermore, the(4R)-4-methyl-4-[2,-(1-methylpyrrol-2-yl)ethyl]-1,3-oxazolidin-2-oneobtained above was analyzed with a HPLC column for separating opticalisomers [ChiralCel OJ (0.46 cm×25 cm), Daicel Chemical Industries, Ltd.,mobile phase: n-hexane/2-propanol (70/30), flow rate: 1.0 ml/min] in asimilar manner to that mentioned in Reference example 11, and itsoptical purity was determined.

From the results of the HPLC analysis, it was confirmed that thecompound eluted first (retention time: 12.49 min) was the 4S-isomer, andthe compound eluted afterward (retention time: 15.48 min) was the4R-isomer, and that the optical purity of this product was 99.7% ee.

According to the results obtained above, the optical purity of the(2R)-2-amino-2-methyl-4-(1-methylpyrrol-2-yl)butan-1-ol ½ D-(−)tartratesynthesized was confirmed to be more than 99.7%.

Melting point: 198–199° C., ¹H-NMR spectrum (CD₃OD, 400 MHz) δ : 6.54(t, 1H, J=2.3 Hz), 5.91 (dd, 1H, J=3.7 Hz, 2.3 Hz), 5.82 (br d, 1H,J=3.7 Hz), 4.32 (s, 1H), 3.61 (d, 1H, J=11.3 Hz), 3.55 (s, 3H), 3.54 (d,1H, J=11.3 Hz), 2.69–2.57 (m, 2H), 1.97 .(ddd, 1H, J=13.8 Hz, 9.4 Hz,7.6 Hz), 1.88 (ddd, 1H, J=13.8 Hz, 11.0 Hz, 6.3 Hz), 1.28 (s, 3H).

IR spectrum ν_(max) cm⁻¹ (KBr) 3480, 3430, 2926, 2634, 2545, 1586, 1516,1389., 1359, 1309, 1291, 1105, 1039, 710, 690.

Mass spectrum (FAB⁺) m/z: 183((M+H)⁺; as the free form of the titlecompound),

Elemental analysis (% as C₁₀H₁₈N₂O.½C₄H₆O₆) Calculated: C, 56.01; H,8.23; N, 10.89; Found: C, 55.81; H, 8.22; N, 10.89.

(19b)(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-(1-methylpyrrol-2-yl)butane

To a suspension of(2R)-2-amino-2-methyl-4-(1-methylpyrrol-2-yl)butan-1-ol ½ D-(−)tartrate(3.98 g, 15.5 mmol) obtained in Reference example (19a) in a mixedsolvent of dichloromethane (50 ml) and water (12.5 ml) was added aqueoussodium hydroxide solution [prepared by dissolving sodium hydroxide (97%pure) (3.20 g) in water (12.5 ml)], and the resulting mixture wasstirred at room temperature for 20 minutes. After stirring., thereaction mixture was extracted with dichloromethane. The extract wasdried over anhydrous sodium sulfate, filtered and evaporated in vacuo.

Subsequently, to the solution of the residue obtained in dichloromethane(78 ml) were added successively triethylamine (21.5 ml, 154.7 mmol),acetic anhydride (7.3 ml, 77.4 mmol) and 4-dimethylaminopyridine (0.1893g, 1.55 mmol), and the resulting mixture was stirred at room temperaturefor 1 hour. After stirring, methanol was added to the reaction mixtureto quench the reaction, and the reaction mixture was evaporated invacuo. Ethyl acetate and water were added to the residue obtained, andthe resulting mixture was extracted with ethyl acetate. The extract waswashed successively with water, saturated aqueous sodiumhydrogencarbonate solution and saturated aqueous sodium chloridesolution and dried over anhydrous sodium sulfate. After filtration, thesolvent was removed in vacuo, and the residue was purified bychromatography on a silica gel column using ethyl acetate as the eluentto afford the title compound (4.23 g, quantitative yield).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 6.54(t, 1H, J=2.4 Hz), 6.04 (t, 1H,J=2.4 Hz), 5.88 (d, 1H, J=2.4 Hz), 5.39 (br s, 1H), 4.33 (d, 1H, J=11.2Hz), 4.20 (d, 1H, J=11.2 Hz), 2.60–2.51 (m, 2H), 2.26–2.19 (m, 1H), 2.09(s, 3H), 1.97–1.89 (m, 4H), 1.38 (s, 3H).

Mass spectrum (FAB⁺) m/z: 267((M+H)⁺), 266(M⁺).

Reference Example 20 (1-Ethylpyrrol-2-yl)methyl triphenylphosphoniumiodide

A mixture of 35% aqueous formaldehyde solution (9 ml, 105 mmol) anddimethylamine hydrochloride (9.0 g, 110 mmol) was added to1-ethylpyrrole (10.0 g, 105 mmol) with stirring under ice-cooling over a90-minute interval, and then the resulting mixture was stirred at roomtemperature for 6 hours. After stirring, 10% aqueous sodium hydroxidesolution (150 ml) was added to the reaction mixture, and the resultingmixture was extracted with ether. The extract was washed with saturatedaqueous sodium chloride solution and dried over anhydrous sodiumsulfate. After filtration, the solvent was removed in vacuo, and theresidue was purified by chromatography on a silica gel column using amixed solvent of dichloromethane and methanol (9:1) as the eluent toafford 2-(N,N-dimethylaminomethyl)-1-ethylpyrrole (15.6 g, yield: 97%).

Subsequently, to a solution of2-(N,N-dimethylaminomethyl)-1-ethylpyrrole (15.6 g, 102 mmol) obtainedabove in ethanol (150 ml) was added methyl iodide (7.7 ml. 124 mmol)with stirring under ice-cooling, and then the resulting mixture wasstirred at room temperature for 3 hours. After stirring, ethyl acetate(150 ml) was added to the reaction mixture. The crystals precipitatedwere collected by filtration, washed with ethyl acetate and dried toafford (1-ethylpyrrol-2-yl)methyl trimethylammonium iodide (20 g, yield:66%).

Subsequently, to a suspension of (1-ethylpyrrol-2-yl)methyltrimethylammonium iodide (20 g, 68.0 mmol) obtained above inacetonitrile (200 ml) was added triphenylphosphine (22.0 g, 83.9 mmol),and the resulting mixture was stirred at 80° C. for 9 hours. Aftercooling, the reaction mixture was concentrated to about one-half of itsinitial volume, to which was added ethyl acetate (100 ml). The crystalsprecipitated were collected by filtration, washed with ethyl acetate anddried in vacuo to afford the title compound (27.5 g,yield: 81%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 7.94–7.89 (m, 3H), 7.78–7.71 (m,6H), 7.64–7.57 (m, 6H), 6.82–6.79 (m, 1H), 5.96–5.92 (m, 1H), 5.51–5.47(m, 1H), 5.10 (d, 2H, J=13.9 Hz), 3.35 (q, 2H, J=7.3 Hz), 0.96 (t, 3H,J=7.3 Hz).

Reference Example 21(2R)-2-t-Butoxycarbonylamino-2-methyl-4-(1-ethylpyrrol-2-yl)-1-n-hexanoyloxy-3-butene

To a suspension of (1-ethylpyrrol-2-yl)methyl triphenylphosphoniumiodide (19.8 g, 39.8 mmol) obtained in Reference example 20 intetrahydrofuran (100 ml) was added a solution of potassium t-butoxide(4.47 g, 39.8 mmol) in tetrahydrofuran (70 ml) with stirring underice-cooling over a 30-minute interval, and the resulting mixture wasstirred under ice-cooling for 1.5 hours.

Subsequently, to the reaction mixture was added a solution of(2S)-2-t-butoxycarbonylamino-3-n-hexanoyloxy-2-methyl-1-propanal (10 g,33.2 mmol) obtained in Reference example (2b) in tetrahydrofuran (50 ml)with stirring under ice-cooling over a 30-minute interval, and theresulting mixture was stirred under ice-cooling for 1.5 hours. Afterstirring, saturated aqueous ammonium chloride solution was added to thereaction mixture to quench the reaction, and then the reactiontemperature was raised to room temperature. After evaporation of thereaction mixture in vacuo, water and ethyl acetate were added to theresidue, and then the resulting mixture was extracted with ethylacetate. The extract was washed successively with water and saturatedaqueous sodium chloride solution and dried over anhydrous sodiumsulfate. After filtration, the solvent was removed in vacuo, and theresidue was purified by chromatography on a silica gel column using amixed solvent of hexane and ethyl acetate (4:1) as the eluent to affordthe title compound (11.7 g, yield: 90%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 6.67–6.62 (m, 2H), 6.42–6.36 (m,1H,), 6.31–6.26 (m, 3H), 6.13–6.08 (m, 2H), 6.02–5.96 (m, 1H), 5.63–5.58(m, 1H), 4.35–4.08 (m, 4H), 3.96–3.86 (m, 4H), 2.85–2.81 (m, 4H),1.67–1.58 (m, 4H), 1.48–1.24 (m, 38H), 0.93–0.86 (m, 6H).

Reference Example 22(4R)-4-Methyl-4-[2-(1-ethylpyrrol-2-yl)ethenyl]-1,3-oxazolidin-2-one

To a solution of(2R)-2-t-butoxycarbonylamino-2-methyl-4-(1-ethylpyrrol-2-yl)-1-n-hexanoyloxy-3-butene(11.7 g, 29.8 mmol) obtained in Reference example 21 in a mixed solventof tetrahydrofuran (40 ml) and methanol (40 ml) was added 2N aqueoussodium hydroxide solution (40 ml), and the resulting mixture was stirredat room temperature for 1.5 hours. After stirring, acetic acid (1.5 ml)was added to the reaction mixture to quench the reaction, and then thereaction mixture was poured into water and extracted with ethyl acetate.The extract was washed successively with water and saturated aqueoussodium chloride solution and dried over anhydrous sodium sulfate. Afterfiltration, the solvent was removed in vacuo to afford the crude product(8.7 g).

Subsequently, to a solution of the crude product obtained above intetrahydrofuran (100 ml) was added a solution of potassium t-butoxide(4.0 g, 35.6 mmol) in tetrahydrofuran (30 ml) with stirring underice-cooling over a 10-minute interval, and the resulting mixture wasstirred at the same temperature for 1 hour. After stirring, the reactionmixture was neutralized with acetic acid (2 ml) and concentrated invacuo. Water and ethyl acetate were added to the residue, and theresulting mixture was extracted with ethyl acetate. The extract waswashed with saturated aqueous sodium chloride solution and dried overanhydrous sodium sulfate. After filtration, the solvent was removed invacuo, and the residue was purified by chromatography on a silica gelcolumn using a mixed solvent of hexane and ethyl acetate (3:2) as theeluent to afford the title compound (5.7 g, yield: 86%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 6.73–6.65 (m, 2H), 6.52–6.46 (m,1H,), 6.36–6.29 (m, 2H), 6.15–6.10 (m, 2H), 6.05–5.97 (m, 2H), 5.69–5.65(m, 2H), 4.31–4.09 (m, 4H), 3.97–3.83 (m, 4H), 1.60–1.53 (m, 6H),1.39–1.31 (m, 6H).

Reference Example 23(4R)-4-Methyl-4-[2-(1-ethylpyrrol-2-yl)ethyl]-1,3-oxazolidin-2-one

To a suspension of 10% palladium-charcoal (50% wet with water) (500 mg)in ethanol (10 ml) was added a solution of(4R)-4-methyl-4-[2-(1-ethylpyrrol-2-yl)ethenyl]-1,3-oxazolidin-2-one(5.7 g, 25.9 mmol) obtained in Reference example 22 in ethanol (50 ml),and the resulting mixture was stirred at room temperature under ahydrogen atmosphere for 1 hour. After stirring, the palladium-charcoalin the reaction mixture was filtered off using celite, and the filtratewas evaporated in vacuo. The residue obtained was purified bychromatography on a silica gel column using a mixed solvent of hexaneand ethyl acetate (3:7) as the eluent to afford the title compound (5.0g, yield: 87%).

Furthermore, the(4R)-4-methyl-4-[2-(1-ethylpyrrol-2-yl)ethyl]-1,3-oxazolidin-2-oneobtained above was analyzed with a HPLC column for separating opticalisomers [ChiralPak OJ (0.46 cm×25 cm), Daicel Chemical Industries, Ltd.,mobile phase: n-hexane/2-propanol (70/30), flow rate: 1.0 ml/min], andits optical purity was determined.

From the results of the HPLC analysis, it was confirmed that thecompound eluted first (retention time: 7.5 min) was the 4S-isomer, andthe compound eluted afterward (retention time: 8.3 min) was the4R-isomer, and that the optical purity of the product synthesized was83.7% ee.

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 6.66–6.63 (m, 1H), 6.10–6.07 (m,1H), 5.89–5.86 (m, 1H), 5.00 (br s, 1H), 4.15 (d, 1H, J=8.1 Hz), 4.08(d, 1H, J=8.1 Hz), 3.84 (q, 2H, J=7.3 Hz), 2.67–2.61 (m, 2H), 1.99–1.92(m, 2H), 1.43 (s, 3H), 1.87 (t, 3H, J=7.3 Hz).

Reference Example 24(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-(1-ethylpyrrol-2-yl)butane (24a)(2R)-2-Amino-2-methyl-4-(1-ethylpyrrol-2-yl)butan-1-ol ½ D-(−)tartrate

To a solution of(4R)-4-methyl-4-[2-(1-ethylpyrrol-2-yl)ethyl]-1,3-oxazolidin-2-one (4.9g, 22.0 mmol) obtained in Reference example 23 in a mixed solvent oftetrahydrofuran (80 ml) and methanol (40 ml) was added 5.5N aqueouspotassium hydroxide solution (40 ml), and the resulting mixture wasrefluxed for 4 days. After cooling, water was added to the reactionmixture, and the resulting mixture was extracted with dichloromethane.The extract was dried over anhydrous sodium sulfate, and afterfiltration, the solvent was removed in vacuo.

Subsequently, to a solution of the residue obtained in ethanol (200 ml)was added a solution of D-(−)-tartrate (1.59 g, 10.5 mmol) in ethanol(20 ml) with stirring, and then the resulting mixture was allowed tostand at room temperature for 4 hours. The crude crystals precipitatedwere collected by filtration and recrystallized from a mixed solvent ofethanol (100 ml) and water (10 ml). The crystals obtained wererecrystallized again from a mixed solvent of ethanol (50 ml) and water(5 ml) to afford the title compound (2.8 g, yield: 37%) as colorlessplate crystals.

Subsequently, to a suspension of(2R)-2-amino-2-methyl-4-(1-ethylpyrrol-2-yl)butan-1-ol ½ D-(−)tartrate(55.5 mg, 0.16 mmol) in dichloromethane (1.6 ml) were added successivelydi-t-butyl dicarbonate (0.17 g, 0.78 mmol), triethylamine (0.22 ml, 1.58mmol) and 4-dimethylaminopyridine (3.0 mg, 0.025 mmol) with stirring,and the resulting mixture was stirred at room temperature for 20minutes.After stirring, water was added to the reaction mixture, and theresulting mixture was concentrated in vacuo. The residue obtained waspurified by chromatography on a silica gel column using a mixed solventof hexane and ethylacetate (1:1) as the eluent to afford(4R)-4-methyl-4-[2-(1-ethylpyrrol-2-yl)ethyl]-1,3-oxazolidin-2-one (18.0mg, yield: 58%).

Furthermore, the(4R)-4-methyl-4-[2-(1-ethylpyrrol-2-yl)ethyl]-1,3-oxazolidin-2-oneobtained above was analyzed with a HPLC column for separating opticalisomers [ChiralPak OJ (0.46 cm×25 cm), Daicel Chemical Industries, Ltd.,mobile phase: n-hexane/2-propanol (70/30), flow rate: 1.0 ml/min], andits optical purity was confirmed to be 99.9%ee.

From the results obtained above, the optical purity of(2R).-2-methyl-2-amino-4-(1-ethylpyrrol-2-yl)butan-1-ol ½ D-(−)tartratesynthesized was confirmed to be more than 99.9%.

¹H-NMR spectrum (DMSO-d₆, 400 MHz) δ : 6.58–6.54 (m, 1H), 5.93–5.89 (m,1H), 5.79–5.76 (m, 1H), 4.27 (s, 1H), 3.85 (q, 2H, J=7.3 Hz), 3.68 (d,1H, J=11.7 Hz), 3.51 (d, 1H, J=11.7 Hz), 2.62–2.56 (m, 2H), 1.99–1.82(m, 2H), 1.29 (t, 3H, J=7.3 Hz), 1.27 (s, 3H).

(24b) (2R)-1-Acetoxy-2-acetylamino-2-methyl-4-(1-ethylpyrrol-2-yl)butane

To a solution of (2R)-2-amino-2-methyl-4-(1-ethylpyrrol-2-yl)butan-1-ol½ D-(−)tartrate (2.7 g, 7.80 mmol) obtained in Reference example (24a)in dichloromethane (30 ml) were added successively triethylamine (17.0ml, 122 mmol), acetic anhydride (7.6 ml, 80.4 mmol) and4-dimethylaminopyridine (20 mg, 0.16 mmol), and the resulting mixturewas stirred at room temperature for 3.5 hours. After stirring, water wasadded to the reaction mixture, and the resulting mixture was extractedwith dichloromethane. The extract was washed successively with water andsaturated aqueous sodium chloride solution and dried over anhydroussodium sulfate. After filtration, the solvent was removed in vacuo, andthe residue was purified by chromatography on a silica gel column usingethyl acetate as the eluent to afford the title compound (2.2 g, yield:96%)

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 6.62–6.59 (m, 1H), 6.09–6.06 (m,1H), 5.89–5.87 (m, 1H), 5.4.1 (br s, 1H.), 4.34 (d, 1H, J=11.0 Hz), 4.21(d, 1H, J=11.0 Hz), 3.85 (q, 2H, J 7.3 Hz), 2.60–2.51 (m, 2H), 2.26–2.18(m, 1H), 2.08 (s, 3H), 1.98–1.93 (m, 1H), 1.92(s, 3H), 1.38 (s, 3H),1.37 (t, 3H, J=7.3 Hz).

Reference Example 25 (1-t-Butoxycarbonylpyrrol-27yl)methyltriphenylphosphonium iodide

A mixture of 35% aqueous formaldehyde solution (3.2 ml, 40.7 mmol) anddimethylamine hydrochloride (3.44 g, 42.4 mmol) was added to pyrrole(2.72 g, 40.47 mmol) at room temperature with stirring over a 20-minuteinterval, and the resulting mixture was stirred at room temperature for2 hours. After stirring, 10% aqueous sodium hydroxide solution (18 ml)was added to the reaction mixture, and the reaction mixture wasextracted with dichloromethane. The extract was washed with saturatedaqueous sodium chloride solution and dried over anhydrous sodiumsulfate. After filtration, the solvent was removed in vacuo, and theresidue was purified by chromatography on a silica gel column using amixed solvent of dichloromethane and methanol (10:1) as the eluent toafford 2-(N,N-dimethylaminomethyl)pyrrole (4.55 g, quantitative yield).

Subsequently, to a solution of 2-(N,N-dimethylaminomethyl)pyrrole (4.54g, 40.41 mmol) obtained above in ethanol (40 ml) was added methyl iodide(3.05 ml, 49.0 mmol) with stirring under ice-cooling, and then theresulting mixture was stirred at room temperature for 7 hours. Afterstirring, ethyl acetate was added to the reaction mixture, and then thecrystals precipitated were collected by filtration and washed with ethylacetate and dried to afford (pyrrol-2-yl)methyl trimethylammonium iodide(7.59 g, yield: 71%).

Subsequently, to a suspension of (pyrrol-2-yl)methyl trimethylammoniumiodide (7.59 g, 28.52 mmol) obtained above in acetonitrile (60 ml) wasadded triphenylphosphine (8.98 g, 34.2 mmol) with stirring, and theresulting mixture was stirred at 80° C. for 6 hours. After cooling, thereaction mixture was concentrated to about one-half of its initialvolume, to which was added ethyl acetate (100 ml). The crystalsprecipitated were collected by filtration, washed with ethyl acetate anddried in vacuo to afford (pyrrol-2-yl)methyl trimethylphosphonium iodide(12.33 g, yield: 92%).

Subsequently, to a suspension of (pyrrol-2-yl)methyltrimethylphosphonium iodide (12.30 g, 26.21 mmol) obtained above inacetonitrile (115 ml) were added successively di-t-butyl dicarbonate(7.61 g, 34.87 mmol) and 4-dimethylaminopyridine (0.16 g, 1.31 mmol)with stirring, and the resulting mixture was stirred at room temperaturefor 24 hours. After evaporation of the reaction mixture in vacuo, ethylacetate (50 ml) and dichloromethane (4 ml) were added to the residuewith stirring, and then the crystals precipitated were collected byfiltration, washed with ethyl acetate and dried in vacuo to afford thetitle compound (14.02 g, yield: 94%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 7.82–7.78 (m, 3H), 7.68–7.58 (m,12H), 7.09–7.07 (m, 1H), 6.42–6.39 (m, 1H), 6.11 (t, 1H, J=3.7 Hz), 5.68(d, 2H, J=13.2 Hz), 1.29 (s, 3H).

Reference Example 26(2R)-2-t-Butoxycarbonylamino-2-methyl-4-(1-t-butoxycarbonylpyrrol-2-yl)-1-n-hexanoyloxy-3-butene

To a suspension of (1-t-butoxycarbonylpyrrol-2-yl)methyltriphenylphosphonium iodide (3.30 g, 5.80 mmol) obtained in Referenceexample 25 in tetrahydrofuran (60 ml) was added a solution of potassiumt-butoxide (0.65 g, 5.8 mmol) in tetrahydrofuran (5.8 ml) with stirringunder ice-cooling, and the resulting mixture was stirred underice-cooling for 15 minutes.

Subsequently, to the reaction mixture was added a solution of(2S)-72-t-7butoxycarbonylamino-3-n-hexanoyloxy-2-methyl-1-propanal (1.46g, 4.83 mmol) obtained in Reference example (2b) in tetrahydrofuran (3ml) with stirring under ice-cooling, and the resulting mixture wasstirred under ice-cooling for 1 hour. After stirring, saturated aqueousammonium chloride solution was added to the reaction mixture to quenchthe reaction, and then the reaction temperature was raised to roomtemperature. To the reaction mixture were added successively water andethyl acetate, and the resulting mixture was extracted with ethylacetate. The extract was washed with saturated aqueous sodium chloridesolution and dried over anhydrous sodium sulfate. After filtration, thesolvent was removed in vacuo, and the residue was purified bychromatography on a silica gel column using a mixed solvent of hexaneand ethyl acetate (5:1) as the eluent to afford the title compound (2.12g, yield: 94%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 7.25–7.20 (m, total 2H), 7.11 (d,1H, J=16.1 Hz), 6.61 (d, 1H, J=12.5 Hz), 6.39–6.24 (m, total 2H),6.18–6.08 (m, total 2H), 6.08 (d, 1H, J=16.1 Hz), 5.64 (d, 1H, J=12.5Hz), 4.92–4.75 (m, total 2H), 4.34–4.23 (m, total 2H), 4.22–4.16 (m,total 2H), 2.38–2.29 (m, total 4H), 1.69–1.20 (m, total 54H), 0.94–0.82(m, total 6H).

IR spectrum ν_(max) cm⁻¹ (CHCl₃): 3445, 2981, 2934, 1734, 1495, 1457,1393, 1370, 1333, 1252, 1163, 1123, 1066.

Mass spectrum (FAB⁺) m/z: 465((M+H)⁺).

Reference Example 27(4R)-4-Methyl-4-[2-(pyrrol-2-yl)ethenyl]-1,3-oxazolidin-2-one

To a solution of(2R)-2-t-butoxycarbonylamino-2-methyl-4-(1-t-butoxycarbonylpyrrol-2-yl)-1-n-hexanoyloxy-3-butene(1.78 g, 3.82 mmol) obtained in Reference example 26 in a mixed solventof tetrahydrofuran (20 ml) and methanol (20 ml) was added 1N aqueoussodium hydroxide solution (20 ml), and the resulting mixture was stirredat room temperature for 1 hour. After stirring, water was added to thereaction mixture, and the resulting mixture was extracted with ethylacetate. The extract was washed with saturated aqueous sodium chloridesolution and dried over anhydrous sodium sulfate. After filtration, thesolvent was removed in vacuo to afford the crude product.

Subsequently, to a solution of the crude product obtained above intetrahydrofuran (60 ml) was added potassium t-butoxide (0.557 g, 4.96mmol) with stirring, and the resulting mixture was stirred at roomtemperature for 1 hour. After stirring, water was added to the reactionmixture, and the resulting mixture was extracted with ethyl acetate. Theextract was washed with saturated aqueous sodium chloride solution anddried over anhydrous sodium sulfate. After filtration, the solvent wasremoved in vacuo, and the residue was purified by chromatography on asilica gel column using a mixed solvent of ethyl acetate and hexane(2:1) as the eluent to afford the title compound (0.259 g, yield: 35%).

¹H-NMR spectrum (CDCl₃, 400 MHz):8.69–8.22 (m, total 2H), 6.88–6.76 (m,total 2H), 6.48 (d, 1H, J=16.1 Hz), 6.34 (d, 1H, J=12.5 Hz), 6.39–6.18(m, total 4H), 5.82 (d, 1H, J=16.1 Hz), 5.47 (br s, 1H), 5.37 (d, 1H,J=12.5 Hz), 5.16 (br s, 1H), 4.40 (d, total 2H, J=8.8 Hz), 4.19 (d,total 2H, J=8.8 Hz), 1.59 (s, 3H), 1.55 (s, 3H).

IR spectrum ν_(max) cm¹ (CHCl₃): 3467, 2976, 2929, 1759, 1637, 1477,1455, 1373, 1280, 1165, 1041, 954, 909.

Mass spectrum (FAB⁺ ) m/z: 192(M⁺).

Reference Example 28(4R)-4-methyl-4-[2-(pyrrol-2-yl)ethyl]-1,3-oxazolidin-2-one

To a solution of(4R)-4-methyl-4-[2-(pyrrol-2-yl)ethenyl]-1,3-oxazolidin-2-one (0.259 g,1.35 mmol) obtained in Reference example 27 in methanol (6 ml) was added10% palladium-charcoal (50% wet with water) (26 mg), and the resultingmixture was stirred at room temperature under a hydrogen atmosphere for30 minutes. After stirring, the palladium-charcoal in the reactionmixture was filtered off using celite. After evaporation of the filtratein vacuo, the residue was purified by chromatography on a silica gelcolumn using a mixed solvent of ethyl acetate and hexane (2:1) as theeluent to afford the title compound (0.238 g, yield: 91%)

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 8.41–8.15 (m, 1H), 6.73–6.68 (m,1H), 6.17–6.10 (m, 1H), 5.96–5.90 (m, 1H), 5.75 (br s, 1H), 4.12 (d, 1H,J=8.8 Hz), 4.05 (d, 1H, J=8.8 Hz), 2.76–2.61 (m 2H.), 2.00–1.83 (m, 2H),1.37 (s., 3H).

IR spectrum ν_(max) cm⁻¹ (CHCl₃): 3472, 2980, 2933, 1754, 1571, 1479,1457, 1400, 1382, 1250, 1162, 1093, 1044, 942.

Mass spectrum-(FAB⁺) m/z: 194(M⁺).

Reference Example 29 5-(4-Fluorophenyl)pent-1-yne

To a suspension of sodium hydride (2.11 g, 48.4 mmol) in drytetrahydrofuran (60 ml) was added dropwise ethyl diethylphosphonoacetate(10.84 g, 48.4 mmol) with stirring under ice-cooling, and the resultingmixture was stirred for 10 minutes.

Subsequently, to the reaction mixture was added dropwise a solution of4-fluorobenzaldehyde (5.00 g, 40.3 mmol) in dry tetrahydrofuran (60 ml)at the same temperature with stirring, and the resulting mixture wasstirred for 3 hours. After stirring, the reaction mixture was pouredinto ice-cold water (150 ml) with stirring and then extracted with ethylacetate. The organic layer was dried over anhydrous magnesium sulfate.After removal of the solvent in vacuo, the residue was purified by flashchromatography on a silica gel column using a mixed solvent of hexaneand ethyl acetate (10:1–3:1) as the eluent to afford ethyl4-fluorocinnamate (6.69 g, yield: 86%) as a colorless oil.

Furthermore, to a solution of the reaction product obtained above (6.52g, 33.6 mmol) in ethyl acetate (100 ml) was added 5% rhodium/alumina(1.30 g), and the resulting mixture was stirred at room temperatureunder a hydrogen atmosphere for 8 hours. After stirring, the reactionmixture was filtered using celite, and the filtrate was evaporated invacuo.

Subsequently, to a suspension of lithium aluminum hydride (1.26 g, 33.2mmol) in dry tetrahydrofuran (60 ml) was added dropwise a solution ofthe residue obtained above in dry tetrahydrofuran (30 ml) with stirringunder ice-cooling, and the resulting mixture was stirred at the sametemperature for 30 minutes. After stirring, saturated aqueous sodiumsulfate solution was added to the reaction mixture, and the resultingmixture was furthermore stirred at room temperature for 10 minutes.After stirring, the reaction mixture was filtered using celite, and thefiltrate was extracted with ethyl acetate. The organic layer was washedwith saturated aqueous sodium chloride solution and dried over anhydrousmagnesium sulfate. After filtration, the solvent was removed in vacuo,and the residue was purified by flash chromatography on a silica gelcolumn using a mixed solvent of hexane and ethyl acetate (5:1–1:1) asthe eluent to afford 3-(4-fluorophenyl)propan-1-ol (4.86 g, yield: 95%)as a colorless oil.

Subsequently, to a solution of 3-(4-fluorophenyl)propan-1-ol (4.83 g,31.3, mmol) obtained above in dichloromethane (50 ml) were addedsuccessively triethylamine (6.55 ml, 47.0 mmol) and methanesulfonylchloride (2.91 ml, 37.6 mmol) with stirring under ice-cooling, and theresulting mixture was stirred under a nitrogen atmosphere for 30minutes. After stirring, the reaction mixture was diluted withdichloromethane (50 ml), washed successively with 10% aqueoushydrochloric acid solution and saturated aqueous sodium chloridesolution, both of which were ice-chilled previously, and dried overanhydrous magnesium sulfate. After filtration, the solvent was removedin vacuo.

Subsequently, to a solution of the residue obtained in acetone (100 ml)was added sodium iodide (9.39 g, 62.6 mmol), and the resulting mixturewas stirred at 50° C. under a nitrogen atmosphere for 2 hours. Afterstirring, the reaction mixture was diluted with ethyl acetate (250 ml),washed successively with 10% aqueous sodium thiosulfate solution andsaturated aqueous sodium chloride solution and dried over anhydrousmagnesium sulfate. After filtration, the solvent was removed in vacuo,and the residue was purified by flash chromatography on a silica gelcolumn using a mixed solvent of hexane and ethyl acetate (5:1–2:1) asthe eluent to afford 3-(4-fluorophenyl)-1-iodopropane (7.12 g,yield:86%) as a pale yellow oil.

Subsequently, sodium acetylide (18% slurry in xylene) (50 ml) was addedto hexamethylphosphoramide (20 ml) with stirring, and to the resultingmixture was furthermore added a solution of3-(4-fluorophenyl)-1-iodopropane (7.00 g, 26.5 mmol) obtained above indry dimethylformamide (20 ml) with stirring under ice-cooling, and thenthe resulting mixture was stirred at room temperature for 2 hours. Afterstirring, ice-cold water was added to the reaction mixture carefullywith stirring under ice-cooling, and the resulting mixture was extractedwith ethyl acetate. The organic layer was washed with saturated aqueoussodium chloride solution and dried over anhydrous magnesium sulfate.After filtration, the solvent was removed in vacuo, and the residue waspurified by flash chromatography on a silica gel column using hexane asthe eluent to afford the title compound (2.67 g, yield: 62%) as acolorless oil.

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 7.14 (m, 2H), 6.97 (m, 2H), 2.71 (t,2H, J=7.5 Hz), 2.19 (m, 2H), 1.99 (t, 1H, J=2.6 Hz), 1.82 (m,2H).

Mass spectrum (EI) m/z: 162(M⁺).

Reference Example 30 5-Phenylpent-1-yne

The title compound was synthesized using 3-phenyl-1-iodopropane andsodium acetylide by conducting the reactions similar to those mentionedin Reference example 29.

¹H-NMR spectrum (CDCl₃, 400 MHz) δ : 7.32–7.26 (m, 2H), 7.23–7.16(m,3H), 2.74 (t, 2H, J=7.6 Hz), 2.21 (dt,2H, J=7.6 Hz, 2.8 Hz), 1.99 (t,1H, J=2.8 Hz), 1.89–1.81 (m, 2H).

Mass spectrum (EI) m/z: 144(M⁺).

Reference Example 31 5-(4-Chlorophenyl)pent-1-yne

The title compound was synthesized using3-(4-chlorophenyl)-1-iodopropane and sodium acetylide by conducting thereactions similar to those mentioned in Reference example 29.

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 7.26–7.23 (m, 2H), 7.13–7.11 (m,2H), 2.71 (t, 2H, J=7.3 Hz), 2.19 (dt, 2H, J=7.3 Hz, 2.9 Hz), 1.99 (t,1H, J=2.9 Hz), 1.85–1.78 (m, 2H).

Reference Example 32 5-(3-Trifluoromethylphenyl)pent-1-yne

The title compound was synthesized using3-(3-trifluoromethylphenyl)-1-iodopropane and sodium acetylide byconducting the reactions similar to those mentioned in Reference example29.

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 7.46–7.37 (m, 4H), 2.81 (t, 2H,J=7.3 Hz), 2.22 (dt, 2H, J=7.3 Hz, 2.9 Hz), 2.01 (t, 1H, J=2.9 Hz),1.90–1.83 (m, 2H).

Reference Example 33 5-Cyclohexylpent-1-yne

The title compound was synthesized using 3-cyclohexyl-1-iodopropane andsodium acetylide by conducting the reactions similar to those mentionedin Reference example 29.

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 2.16 (dt, 2H, J=7.2 Hz, 2.8, Hz),1.94 (t, 1H, J=2.8 Hz), 1.59–1.48 (m, 2H), 1.38–0.75 (m, 13H).

Mass spectrum (EI) m/z 150(M⁺).

Reference Example 34 4-Cyclohexyloxybut-1-yne

To a solution of cyclohexanone (32 ml, 0.31 mol) in dry dichloromethane(950 ml) were added successively 1,3-propanediol (33.5 ml, 0.46 mol),triethyl orthoformate (51.5 ml, 0.31 mol) and zirconium chloride (1.44g, 6.18 mmol) with stirring, and the resulting mixture was stirred atroom temperature under a nitrogen atmosphere for 1 hour. After stirring,ice-chilled 1N aqueous sodium hydroxide solution (1.5 l) was added tothe reaction mixture with stirring, and the resulting mixture wasextracted with dichloromethane. The extract was washed with water anddried over anhydrous sodium sulfate. After filtration, the solvent wasremoved in vacuo, and the residue was purified by reduced-pressuredistillation to afford cyclohexanone trimethylene ketal (26.8 g, yield:55%).

Subsequently, to a suspension of zirconium chloride (24.9 g, 0.11 mol)in tetrahydrofuran (500 ml) was added slowly sodium borohydride (20.5 g,0.54 mol) in portions with stirring under a nitrogen atmosphere, and theresulting mixture was stirred at room temperature for 20 minutes. Afterstirring, to the reaction mixture was added dropwise a solution ofcyclohexanone trimethylene ketal (16.9 g, 0.11 mol) obtained above intetrahydrofuran (170 ml) with stirring while ice-cooling under anitrogen atmosphere, and then the resulting mixture was stirred at roomtemperature for one day. After stirring, to the reaction mixture wasadded ice-chilled 2N hydrochloric acid (600 ml) with stirring underice-cooling to quench the reaction, and then the tetrahydrofuran wasevaporated in vacuo. The aqueous layer which remained was extracted withethyl acetate, and the extract was washed with saturated aqueous sodiumchloride solution and dried over anhydrous sodium sulfate. Afterfiltration, the solvent was removed in vacuo, and the residue waspurified by chromatography on a silica gel column using a mixed solventof hexane and ethyl acetate (10:1–5:2) as the eluent to afford3-cyclohexyloxypropan-1-ol (13.4 g, yield: 78%).

Subsequently, to a solution of 3-cyclohexyloxypropan-1-ol (11.5 g, 72.9mmol) obtained above in dichloromethane (240 ml) were added successivelymolecular sieves 4A (58 g) and pyridinium dichromate (23.8 g, 0.11 mol)with stirring under ice-cooling, and the resulting mixture was stirredat the same temperature under a nitrogen atmosphere for 1 hour and 40minutes. After stirring, ether was added to the reaction mixture, andthe resulting mixture was filtered using celite, which was washed withether. The filtrate and the washings were combined and evaporated invacuo, and the residue was purified by chromatography on a silica gelcolumn using a mixed solvent of hexane and ethyl acetate (20:1–10:1) asthe eluent to afford the crude 3-cyclohexyloxypropionaldehyde (8.60 g).

Subsequently, to a solution of carbon tetrabromide (36.5 g, 0.11 mol) indichloromethane (120 ml) was added a solution of triphenylphosphine.(57.7 g, 0.22 mol) in dichloromethane (120 ml) with stirring whileice-cooling under a nitrogen atmosphere, and the resulting mixture wasstirred for 5 minutes. After stirring, to the reaction mixture was addeda solution of the crude 3-cyclohexyloxypropionaldehyde (8.60 g) obtainedabove in dichloromethane (90 ml) with stirring while ice-cooling under anitrogen atmosphere, and the resulting mixture was stirred at the sametemperature for 25 minutes. After stirring, the reaction mixture wasdiluted with dichloromethane and washed successively with saturatedaqueous sodium hydrogencarbonate solution and saturated aqueous sodiumchloride solution and dried over anhydrous sodium sulfate. Afterfiltration, the solvent was removed in vacuo, and the residue waspurified by chromatography on a silica gel column using a mixed solventof hexane and ethyl acetate (100:1–33:1) as the eluent to afford4-cyclohexyloxy-1,1-dibromobut-1-ene (12.6 g, overall yield in twosteps: 55%).

Furthermore, to a solution of 4-cyclohexyloxy-1,1-dibromobut-1-ene (12.6g, 40.4 mmol) obtained above in tetrahydrofuran (130 ml) was added a1.5M solution of n-butyllithium in hexane (54 ml, 81.0 mmol) at −78° C.with stirring under a nitrogen atmosphere, and the resulting mixture wasstirred at −78° C. for 1 hour. After stirring, the reaction temperaturewas raised slowly to room temperature with stirring, and the reactionmixture was stirred furthermore at room temperature for 50 minutes.After stirring, water was added to the reaction mixture with stirringunder ice-cooling to quench the reaction, and then the resulting mixturewas extracted with ether. The extract was washed with saturated aqueoussodium chloride solution and dried over anhydrous sodium sulfate. Afterfiltration, the solvent was removed in vacuo, and the residue waspurified by chromatography on a silica gel column using a mixed solventof hexane and ethyl acetate (100:1–50:1) as the eluent to afford thetitle compound (4.35 g, yield: 71%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 3.59 (t, 2H, J 7.2 Hz), 3.32–3.23(m, 1H), 2.45 (dt, 2H, J=7.2 Hz, 2.8 Hz), 1.97 (t, 1H., J=2.8 Hz),1.95–1.85 (m, 2H)! 1.81–1.67 (m, 2H), 1.58–1.48 (m, 1H), 1.36–1.13 (m,5H).

Mass spectrum (EI) m/z: 153((M+H)⁺).

Reference Example 35 4-(4-Fluorophenyloxy)but-1-yne

To a solution of 4-fluorophenol (5.00 g, 44.6 mmol), 3-butyn-1-ol (3.38ml, 44.6 mmol) and triphenylphosphine (17.5 g, 66.9 mmol) intetrahydrofuran (100 ml) was added diethyl azodicarboxylate (11.7 g,66.9 mmol) with stirring under ice-cooling, and then the resultingmixture was stirred at room temperature for 18 hours. After stirring,thereaction mixture was evaporated in vacuo, and to the residue were addedhexane (200 ml) and ethyl acetate (20 ml). The precipitate separated outwas filtered off, and the filtrate was evaporated in vacuo. The residueobtained was purified by flash chromatography on a silica gel columnusing hexane as the eluent to afford the title compound.

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 7.02–6.94 (m, 2H), 6.90–6.82 (m,2H), 4.07 (t, 2H, J=7.0 Hz), 2.70–2.63 (m, 2H), 2.05 (t, 1H, J=2.7 Hz).

Mass spectrum (EI) m/z: 164(M⁺).

Reference Example 36 4-Phenyloxybut-1-yne

The title compound was synthesized using phenol and 3-butyn-1-ol byconducting a reaction similar to that mentioned in Reference example 35.

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 7.29 (dd, 2H, J=8.8 Hz, 7.3 Hz),6.96 (t, 1H, J=7.3 Hz), 6.92 (d, 2H, J=8.8 Hz), 4.11 (t, 2H, J=6.6 Hz),2.6,8 (dt, 2H, J=6.6 Hz, 2.2 Hz), 2.04 (t, 1H, J=2.2 Hz).

Reference Example 37 3-(3,4-Dimethylphenyloxy)-1-propyne

The title compound was synthesized using 3,4-dimethylphenol andpropargyl alcohol by conducting a reaction similar to that mentioned inReference example 35.

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 7.04 .(d, 1H, J=8.0 Hz), 6.78 (d,1H, J=2.4 Hz), 6.72 (dd, 1H, J=8.0 Hz, 2.4 Hz), 4.65 (d, 2H, J=2.4 Hz),2.49 (t, 1H, J=2.4 Hz), 2.24 (s, 3H), 2.20 (s, 3H).

Mass spectrum (EI) m/z: 160(M⁺).

Reference Example 38 3-(4-Methylphenyloxy)-1-propyne

The title compound was synthesized using 4-methylphenol and propargylalcohol by conducting a reaction similar to that mentioned in Referenceexample 35.

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 7.10 (d, 2H, J=8.4 Hz), 6.88 (d, 2H,J=8.4 Hz), 4.67 (d, 2H, J=2.4 Hz), 2.50 (t, 1H, J=2.4 Hz), 2.29 (s, 3H).

Mass spectrum (EI) m/z: 146(M⁺).

Reference Example 39 3-(4-Methylthiophenyloxy)-1-propyne

The title compound was synthesized using 4-methylthiophenol andpropargyl alcohol by conducting a reaction similar to that mentioned inReference example 35.

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 7.27 (d, 2H, J=8.9 Hz), 6.93 (d, 2H,J=8.9 Hz), 4.68 (d, 2H, J=2.4 Hz), 2.52 (t, 1H, J=2.4 Hz), 2.45 (s, 3H).

Mass spectrum (EI) m/z: 178(M⁺).

Reference Example 402-[4-(Cyclohexylmethoxy)phenyl]-4,4,5,5-tetramethyl-[1,3,2]-dioxaborolane

To a solution of 4-bromophenol (6.0 g, 34.7 mmol),cyclohexylmethylphenol (4.3 ml, 34.7 mmol) and triphenylphosphine (9.1g, 34.7 mmol) in tetrahydrofuran (100 ml) was added slowly a 40%solution of diethyl azodicarboxylate in toluene (15.1 ml, 34.7 mmol) inportions at 0° C. with stirring, and then the resulting mixture wasstirred at room temperature for 3 hours. After stirring, the reactionmixture was evaporated in vacuo, and hexane was added to the residue.After filtration, the filtrate was evaporated in vacuo once again, andthe residue was purified by chromatography on a silica gel column usinga mixed solvent of ethyl acetate and hexane (1:20) as the eluent toafford 1-bromo-4-(cyclohexylmethoxy)benzene (5.1 g, yield: 54%).

Subsequently, 1-bromo-4-(cyclohexylmethoxy)benzene (3.0 g, 11.1 mmol)obtained above, bis(pinacolato)diborane (3.4 g, 13.3 mmol), palladiumchloride-diphenylphosphinoferrocene complex (450 mg, 0.551 mmol) andpotassium acetate (2.2 g, 22.2 mmol) were dissolved in dimethylsulfoxide (50 ml) and stirred at 80° C. for 30 minutes. After stirring,the reaction mixture was diluted with ethyl acetate, and charcoal wasadded to the resulting mixture. The resulting mixture was stirred atroom temperature for 30 minutes. After filtration, the solvent wasremoved in vacuo, and the residue was purified by chromatography on asilica gel column using a mixed solvent of ethyl acetate and hexane(1:100) as the eluent to afford the title compound (1.72 g, yield: 49%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 7.73 (d, 2H, J=8.5 Hz), 6.88 (d, 2H,J=8.5 Hz), 3.77 (d, 2H, J=5.9 Hz), 1.93–1.64 (m, 5H), 1.33 (s, 12H),1.33–1.14 (m, 4H), 1.12–0.97 (m, 2H).

Reference Example 412-[3-(2-Cyclohexylethoxy)phenyl]-4,4,5,5-tetramethyl-[1,3,2]-dioxaborolane

To a solution of 3-bromophenol (15.0 g, 86.7 mmol),2-cyclohexylethylphenol (12.0 ml, 86.7 mmol) and triphenylphosphine(23.0 g, 86.7 mmol) in tetrahydrofuran (200 ml) was added slowly a 40%solution of diethyl azodicarboxylate in toluene (38.0 ml, 86.7 mmol) inportions at 0° C. with stirring, and then the resulting mixture wasstirred at room temperature for 7 hours. After stirring, the reactionmixture was evaporated in vacuo, and hexane was added to the residue.After filtration, the filtrate was evaporated in vacuo once again, andthe residue was purified by chromatography on a silica gel column usinga mixed solvent of ethyl acetate and hexane (1:100) as the eluent toafford 1-bromo-3-(2-cyclohexylethoxy)benzene (23.0 g, yield: 94%).

Subsequently, 1-bromo-3-(2-cyclohexylethoxy)benzene (5.0 g, 17.7 mmol)obtained above, bis(pinacolato)diborane (5.4 g, 21.2 mmol), palladiumchloride-diphenylphosphinoferrocene complex (1.40 g, 1.77 mmol) andpotassium acetate (3.5 g, 35.4 mmol) were dissolved in dimethylsulfoxide (80 ml) and stirred at 80° C. for 30 minutes. After stirring,the reaction mixture was diluted with ethyl acetate, and charcoal wasadded to the resulting mixture, and then the resulting mixture wasstirred at room temperature for 30 minutes. After filtration, thesolvent was removed in vacuo, and the residue was purified bychromatography on a silica gel column using a mixed solvent of ethylacetate and hexane (1:100) as the eluent to afford the title compound(4.70 g, yield: 80%).

¹H-NMR spectrum (CDCl₃, 400 MHz) δ: 7.38–7.24 (m, 3H), 7.00 (dd, 1H,J=8.1, 2.9 Hz), 4.02 (t, 2H, J=6.6 Hz), 1.81–1.63 (m, 8H), 1.34 (s,12H), 1.31–1.12 (m, 3H), 1.06–0.88 (m, 2H).

Reference Example 42 4-Phenyloxybutanoyl chloride (42a)4-Phenyloxybutanoic acid

To a suspension of sodium hydride (content: 60%) (2.41 g, 60.3 mmol) inN,N-dimethylformamide (60 ml) was added a solution of phenol (5.70 g,60.0 mmol) in N,N-dimethylformamide (30 ml) over a 20-minute intervalwith stirring while ice-cooling under a nitrogen atmosphere, and thenthe resulting mixture was stirred at room temperature for 1.5 hours.After stirring, to the reaction mixture was added a solution ofγ-butyrolactone (5.01 g, 58.2 mmol) in N,N-dimethylformamide (30 ml),and the resulting mixture was stirred at 130° C. for 6 hours. Aftercooling, the reaction mixture was evaporated in vacuo.

Subsequently, water was added to the residue, and the resulting mixturewas partitioned with dichloromethane to separate the aqueous layer. Thedichloromethane layer was washed with water. The washings and theaqueous layer separated above were combined, and acidified with 1Nhydrochloric acid (72 ml), and then extracted with ethyl acetate. Theextract was washed successively with water and saturated aqueous sodiumchloride solution and dried over anhydrous magnesium sulfate. Afterfiltration, the solvent was removed in vacuo, and the residue waspurified by chromatography on a silica gel column using a mixed solventof hexane and ethyl acetate (5:1–2:l) as the eluent to afford the titlecompound (3.58 g, yield: 34%). ¹H-NMR spectrum (CDCl₃, 400 MHz) δ:7.30–7.27 (m, 2H), 6.96–6.87 (m, 3H), 4.03 (t, 2H, J=5.9 Hz), 2.60 (t,2H, J=7.3Hz), 2.16–2.09 (m, 2H)

(42b) 4-Phenyloxybutanoyl Chloride

To a solution of 4-phenyloxybutanoic acid (0.5066 g, 2.81 mmol) obtainedin Reference example (42a) in benzene (5 ml) were added successivelythionyl chloride (0.42 ml, 5.76 mmol) and N,N-dimethylformamide (2 μl),and the resulting mixture was stirred at 80° C. for 1 hour. Aftercooling, the reaction mixture was evaporated in vacuo to afford thetitle compound (0.5556 g, yield: 99%).

Test Example 1

Determination of Inhibitory Activities of Compounds against Host VersusGraft Reaction in Rats

(1) Two strains of rats [Lewis rats (male, 6 weeks of age, Charles RiverJapan Inc.) and WKAH/Hkm rats (male, 7 weeks of age, Japan SLC Inc.)were used. Five rats/group were used.

(2) Induction of HvGR

Spleen cells were isolated from the spleens of WKAH/Hkm and Lewis ratsand floated in RPMI1640 medium (Life Technologies Inc.) at aconcentration of 1×10⁸ cells/ml. 0.1 ml of the medium containing thefree-floating spleen cells of WKAH/Hkm rats or Lewis rats (1×10⁷ of thespleen cells) was then intracutaneously injected into the bilateralfoot-pads of hindlimbs of Lewis rats.

(3) Administration of the Compounds

Compounds were suspended in 0.5% tragacanth solution. The suspendedcompounds were orally administered to rats in the drug-treated group(Lewis rats injected with spleen cells of WKAH/Hkm rats and treated withthe compound) at a volume of 5 ml/kg once daily for 4 successive daysstarting on the day of spleen cell injection. The tragacanth solution(0.5%) was orally administered, instead of the compound-suspendedsolution, to rats in the “same strain group” (Lewis rats injected withspleen cells of Lewis rats) and the control group (Lewis rats injectedwith spleen cells of WKAH/Hkm rats and not treated with the compound).

(4) Determination of Inhibitory Activities of Compounds against HvGR

Average weight of the popliteal lymph nodes of the same strain rats wassubtracted from individual weights of the popliteal lymph nodes ofindividual rats (“HvGR-induced changes in weight of the popliteal lymphnodes”). The inhibitory activities of compounds were calculated from the“HvGR-induced changes in weights of the popliteal lymph nodes” ofindividual rats in the drug-treated group versus the average“HvGR-induced changes in weights of the popliteal lymph nodes” in thecontrol group. The inhibitory activities of compounds were expressed asID₅₀ values (mg/kg) as calculated by least squares method based on thedoses of compounds administered and inhibitory activities at thesedoses.

From the present experiments, compounds of the present inventionexhibited excellent inhibitory activities.

TABLE 9 Compound HvGR ID₅₀ values (mg/kg) Example 2 0.714 Example 30.116 Example 9 0.120 Example 10 0.276 Example 15 0.304 Example 19 0.097Example 20 0.082 Example 33 0.013

Test Example 2

Determination of Inhibitory Activities of Compounds againstAdjuvant-Induced Arthritis

(1) Preparation of Adjuvant

Adjuvant was prepared by suspension of killed Mycobacterium butyricum inmineral oil at a concentration of 2 mg/ml, followed by application ofultrasonic waves.

(2) Preparation of Test Compound

Test compounds were suspended or dissolved in 0.5% tragacanth solution.

(3) Induction of Adjuvant Arthritis

0.05 ml of adjuvant solution prepared as described in (1) wasintracutaneously injected into the right foot-pad of rats (usually Lewisrats). Five rats/group were usually used. Adjuvant was not injected inone group of rats (normal group).

(4) Administration of Compound

Compounds prepared as described in (2) were orally administered to ratsat a volume of 5 ml/kg once daily for 21 successive days. 0.5%tragacanth solution was similarly administered to rats in one groupinjected adjuvant (control group) and a group not injected adjuvant.

(5) Calculation of Inhibitory Activities of Compounds against AdjuvantArthritis

One day after the final drug administration, the foot volume of each ratwas measured by an apparatus for determination of the volume. Theaverage value in normal rats was subtracted from the individual valuesin the drug-treated and control groups. The difference was expressed asthe swelling volume. Inhibitory rate of the compound was calculated fromthe ratio of the individual swelling volume of the rat treated with thecompound to the average swelling volume in the control group.

Inhibitory activities of compounds were expressed as ID₅₀ values (mg/kg)calculated by least squares method based on the doses of the compoundand their inhibitory ratios.

From the present experiments, compounds of the present inventionexhibited excellent inhibitory activities.

TABLE 10 Compound ID₅₀ values (mg/kg) Example 2 0.0899 Example 3 0.0774Example 19 0.108 Example 20 0.102 Example 33 0.0941

Test Example 3

Determination of Inhibitory Activities of Compounds against HvGR (HostVersus Graft Reaction) in Rats

(1) Two strains of rats (Lewis rats (male, 6 weeks of age, Charles RiverJapan Inc.) and WKAH/Hkm rats (male, 7 weeks of age, Japan SLC Inc.)were used. Five rats/group were used.

(2) Induction of HvGR

Spleen cells were isolated from the spleens of WKAH/Hkm rats or Lewisrats and floated in RPMI1640 medium (Life Technologies Inc.) at aconcentration of 1×10⁸ cells/ml. 0.1 ml of the medium containing thefree-floating spleen cells of WKAH/Hkm rats or 0.1 ml of the mediumcontaining the free-floating spleen cells of Lewis rats wereintracutaneously injected into the bilateral foot-pads of hindlimbs ofLewis rats.

(3) Administration of Compounds

Cyclosporin A, tacrolimus and Exemplification compound number 1-1093having formula (Ia-3){2-methyl-4-{5-[5-phenylpentanoyl]thiophen-2-yl}butan-1-ol} maleate(hereinafter expressed as Compound A) were suspended in 0.5% tragacanthsolution at concentrations of 0.08 mg/5 ml, 0.08 mg/5 ml, and 0.008 mg/5ml.

Cyclosporin A suspended solution and the compound suspended solutionwere orally co-administered to rats in the cyclosporin A plus compoundgroup, while tacrolimus suspended solution plus compound suspendedsolution were orally co-administered to rats in the tacrolimus pluscompound group, at a volume of 5 ml/kg once daily for 4 successive days.

Furthermore, Cyclosporin A suspended solution and 0.5% tragacanthsolution, tacrolimus and 0.5% tragacanth solution, or compound A and0.5% tragacanth solution were orally co-administered at a volume of 5ml/kg once daily for 4 successive days, in the cyclosporin A,tacrolimus, or compound A administered groups, respectively.

In both the “same strain group” (Lewis rats treated with spleen cells ofLewis rats but not with the compounds) and “control group” (Lewis ratstreated with the spleen cells of WKAH/Hkm rats but not with thecompounds), 0.5% tragacanth solution was orally administered.

(4) Determination Methods of Inhibitory Activity of Compounds againstHvGR

The average weight of the popliteal lymph nodes in the same strain groupwas subtracted from individual weights of the popliteal lymph nodes inindividual rats (“HvGR-induced changes in the popliteal lymph nodeweights”). The inhibitory activities of the compounds were calculatedfrom the “HvGR-induced changes in the popliteal lymph node weights” ofindividual rats in drug-treated group versus the average “HvGR-inducedchanges in the popliteal lymph node weights” in the control group.

TABLE 11 HvGR Inhibitory Rate Group (%) Cyclosporin A administered group18.7 Tacrolimus administered group 25.8 Compound A administered group16.0 Cyclosporin A + Compound A administered 36.1 group Tacrolimus +Compound A administered group 44.8

Test Example 4

Determination of Inhibitory Activities of Compounds against Mice GvHD(Graft Versus Host Disease)

(1) Two strains of mice. [BDF1 mice (male, 6 weeks of age, Charles RiverJapan Inc.) and C57BL/6 mice (male, 7 weeks of age, Charles River JapanInc.)] were used. Five mice/group (hosts) were used.

(2) Induction of GvHD

Spleen cells were isolated from the spleens of C57BL/6 mice or BDF1 miceand floated in RPMI1640 medium (Life Technologies Inc.) at aconcentration of 2×10⁷ cells/ml. 0.5 ml of the medium containing thefree-floating spleen cells of C57BL/6 mice) was intravenously injectedinto the tail vein of BDF1 mice (GvHD induction group) and the samevolume of the medium containing free-floating spleen cells of BDF1 micewas intravenously injected into the tail vein of BDF1 mice (the “samestrain group”).

(3) Administration of Compounds

Cyclosporin A, tacrolimus, and Exemplification compound number 1-1093having formula (Ia-2){2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol} hydrochloride (hereinafter expressed as Compound B) wassuspended in 0.5% methylcellulose (MC) solution at concentrations of 0.1mg/10 ml, 0.2 mg/10 ml, and 0.01 mg/10 ml.

Cyclosporin A suspended solution and compound B suspended solution wereorally co-administered to mice in the cyclosporin A plus compound Bgroup, while tacrolimus suspended solution and compound B suspendedsolution were orally co-administered to mice in the tacrolimus pluscompound B group, at a volume of 10 ml/kg once daily for 10 successivedays.

Cyclosporin A suspended solution plus 0.5% MC solution, tacrolimus plus0.5% MC solution, and compound B plus 0.5% MC solution were orallyco-administered at a volume of 10 ml/kg once daily for 10 successivedays starting on the day of injection of spleen cells in the cyclosporinA, tacrolimus, and compound B administered groups, respectively.

In both the “same strain group” (BDF1 mice treated with spleen cells ofBDF1 mice but not treated with the compound) and “control group” (BDF1mice injected spleen cells of C57BL/6 mice, but not treated with thecompound), 0.5% MC solution was orally administered.

(4) Determination Methods of Inhibitory Activities of Compounds againstGvHD

Body weight was determined and spleens were weighed, and “spleen weightcompensated for the body weight following injection of GvHD” wascalculated by dividing the spleen weight by the body weight. Average“spleen weight compensated for body weight in the same strain group” wassubtracted from the individual “spleen weight compensated for bodyweight following injection of GvHD”. The inhibitory activities ofcompounds were calculated from the ratios of individual “spleen weightcompensated for body weight following injection of GvHD” to the average“spleen weight compensated for body weight following injection of GvHD”in the control group.

TABLE 12 GvHD Inhibitory Rate Group (%) Cyclosporin A administered group12.5 Tacrolimus administered group 7.6 Compound B administered group−2.9 Cyclosporin A + Compound B administered 28.4 group Tacrolimus +Compound B administered group 13.4

Test Example 5

Determination of Inhibitory Activities of Compounds against RejectionResponse against Skin Transplantation of Mice

(1) Two strains of mice [C57BL/6N mice (female, 5 weeks of age, CharlesRiver Japan Inc.) and BALB/cAnN mice (female, 5 weeks of age, CharlesRiver Japan Inc.)] were used. Ten mice/group (transplanted individuals)were used.

(2) Skin Transplantation Procedures

C57BL/6N mice were sacrificed by cervical dislocation and their skinsremoved. The skins were cut to 8-mm diameter sizes by biopsy punch(MK706, 8 mm, Kai Industries Co., Ltd.). Next, 8 mm diameter sections ofthe back skins of BALB/cAnN mice anaesthetized with Avertin were removedby biopsy punch. The skin was cut along the edge of the damaged area byfine ophthalmic scissors. The previously cut skins of C57BL/6N mice weretransplanted to the removed areas of the skin in BALB/cAnN mice. Thetransplanted areas were fixed with Aron Alpha (Sankyo Co., Ltd.).Sofratulle [10.8 mg of fradiomycin was contained in one piece (10 cm×10cm), Aventis Pharma Ltd.] and sterilized gauze were applied to thetransplanted area of the skin, which was bound with a sterilized bandage(S size, Sumitomo 3M Co., Ltd.) of which both edges were fixed withSILKYTEX (Type 1, ALCARE Co., Ltd.).

(3) Administration of Compounds

Cyclosporin A, tacrolimus and Exemplification compound number 1-1093having formula (Ia-2){2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol} hydrochloride (hereinafter expressed as Compound B) wassuspended in 0.5% methylcellulose (MC) solution at concentrations of 30mg/10 ml, 3 mg/10 ml, and 0.1 mg/10 ml.

Cyclosporin A suspended solution and compound B suspended solution wereorally co-administered to mice in the cyclosporin A and compound Bgroup, while tacrolimus suspended solution and compound B suspendedsolution were orally co-administered to mice in the tacrolimus andcompound B group, at a volume of 10 ml/kg once daily for 14 successivedays starting on the day of transplantation.

(4) Determination Methods of Inhibitory Activities of Compounds againstRejection Responses to Transplanted Skin

On the 6th day after transplantation (the day of transplantation wasdefined as day 0), the Coban, SYLKYTEX, sterilized gauze, and Sofratullewere gently removed paying attention not to damage the skin by a pair ofscissors. From the next day to 20 days after transplantation, it wasdetermined whether rejection responses occurred in the transplantedskin. This determination was carried out blind, and the median day whenthe rejection response occurred was calculated.

TABLE 13 Median Day of Rejection Group Response (Days) 0.5% MCadministered group 10.0 Cyclosporin A administered group 12.0 Tacrolimusadministered group 11.0 Compound B administered group 15.0 CyclosporinA + Compound B administered 17.5 group Tacrolimus + Compound Badministered group 16.5

Formulation Example 1

Tablets Cyclosporin A 50.0 mg Compound A 10.0 mg Lactose 113.0 mg Cornstarch 25.0 mg Magnesium stearate 2.0 mg 200 mg

Powders of the ingredients listed above are mixed and tableted with atableting machine to prepare tablets containing 200 mg of the aboveingredients/tablet.

Compound A in the above formulation is2-amino-2-methyl-4-[5-(5-phenylpentanoyl] thiophen-2-yl]butan-1-olmaleate.

The compounds and the pharmaceutical compositions of the presentinvention exerted potent immunosuppressive activity and showed lowtoxicity. Since the pharmaceutical compositions of the present inventionpotentiated the pharmacological action of each immunosuppressantcontained in the pharmaceutical composition and reduced adverse eventselicited by the individual immunosuppressants, the pharmaceuticalcompositions of the present invention are useful as pharmaceuticalagents. Thus the pharmaceutical compositions of the present inventionare useful as preventive or therapeutic agents for warm-blooded animals(particularly humans) for the following autoimmune diseases or otherimmunology-related diseases such as rejection caused by transplantationof various organs or skin, systemic lupus erythematosus, rheumatoidarthritis, polymyositis, fibrositis, skeletal muscle inflammation,arthrosteitis, osteoarthritis, dermatomyositis, scleoderma, Behcet'ssyndrome, Crohn's disease, ulcerative colitis, autoimmune hepatitis,aplastic anemia, idiopathic thrombocytopenic purpura, autoimmunehemolytic anemia, multiple sclerosis, autoimmune bullosis, psoriasisvulgaris, vasculitis syndrome, Wegener's granuloma, uveitis, Sjögren'ssyndrome, idiopathic interstitial pneumonia, Goodpasture's syndrome,sarcoidosis, allergic granulomatous angitis, bronchial asthma,myocarditis, cardiomyopathy, aortitis syndrome, post myocardialinfarction syndrome, primary pulmonary hypertension, minimal changenephrotic syndrome, membranous nephropathy, membranoproliferativeglomerulonephritis, focal glomerular sclerosis, crescenticglomerulonephritis, myasthenia gravis, inflammatory neuropathy, atopicdermatitis, chronic actinic dermatitis, photosensitivity, pressuresores, Sydenham's chorea, sclerosis, adult-onset type diabetes mellitus,insulin dependent diabetes mellitus, juvenile diabetes mellitus,atherosclerosis, glomerular nephritis, IgA nephropathy,tubulointerstitial nephritis, primary biliary cirrhosis, primarysclerosing cholangitis, fulminant hepatitis, viral hepatitis, GVHD,contact dermatitis, and sepsis.

Furthermore, the pharmaceutical compositions of the present inventionare useful for diseases of infection by fungus, mycoplasma, virus, andprotozoan and the like; cardiovascular diseases such as cardiac failure,cardiac hypertrophy, arrhythmia, angina pectoris, cardiac ischemia,arterial embolism, aneurysm, varix, and circulation disorders; braindiseases such as Alzheimer's disease, dementia, Parkinson's disease,stroke, brain infarction, brain ischemia, depression, manic-depressiveillness, schizophrenia, Huntington's chorea, epilepsy, convulsion,attention deficit disorder, encephalitis, cerebral meningitis, loss ofappetite, and hyperphagia; and various diseases such as lymphoma,leukemia, diuresis, pollakisuria, and diabetic retinopathy.Particularly, the pharmaceutical compositions of the present inventionare useful as preventive or therapeutic agents for autoimmune diseasessuch as rejection caused by transplantation of various organs or skin,systemic lupus erythematosus, rhematoid arthritis, multiple sclerosis,and atopic dermatitis.

The doses and the ratio of (i) the at least one immunosuppressantdefined hereinabove and (ii) the at least one compound selected from thegroup consisting of the compound of the formula (I), a pharmacologicallyacceptable salt thereof and a pharmacologically acceptable esterthereof, which are the active ingredients of compositions of the presentinvention, may vary depending on a variety of conditions, such asactivity of each medicament, and the symptoms, age or weight of thepatient.

The doses of both (i) the immunosuppressant and (ii) the compound of theformula (I) (or said salt or ester) may widely vary depending on thesymptoms, age of the patients, and so on. In the case of oraladministration, the dose of the compound of the formula (I) (or saidsalt or ester) is normally within the range of from 0.05 mg (preferablyfrom 5 mg) to 200 mg (preferably to 40 mg), for an adult human and isadministered one to six times per day depending on the symptoms of thepatients, respectively. In the case of intravenous injection, the doseof the compound of the formula (I) (or said salt or ester) is normallywithin the range of from 0.01 mg (preferably from 1 mg) to 100 mg(preferably to 10 mg), for an adult human and is administered one to sixtimes per day depending on the symptoms of the patients, respectively.

The ratio of the doses of (i) the at least one immunosuppressant and(ii) the compound of the formula (I) (or said salt or ester) can bewidely varied, but the ratio is normally within the range of from 1:500to 500:1 by weight.

In the present invention, the aforesaid active ingredients (i) and (ii)can be administered together either in a single composition, separatelyat the same time, i.e., simultaneously, or separately at differenttimes, in the doses and ratio of doses described above.

When the compounds of the formula (1) (or said salt or ester) are usedin conjunction with an immunosuppressant, X represents not only anoxygen atom or a group of the formula ═N—D, but also a sulfur atom.

1. A compound of formula (Ia)

wherein R¹ and R² are each a hydrogen atom; R³ is a hydrogen atom; R⁴ is a C₁–C₂ alkyl group; n is 2; X is ═N—D, wherein D is a hydrogen atom, a C₁–C₄ alkyl group or a phenyl group; Y is an ethylene group, an ethynylene group, a group of a formula —CO—CH₂ or a phenylene group; Z is an ethylene group or a trimethylene group; R⁵ is an unsubstituted C₃–C₁₀ cycloalkyl group, an unsubstituted C₆–C₁₀ aryl group, or a C₃–C₁₀ cycloalkyl group or a C₆–C₁₀ aryl group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group and a lower alkoxy group; R⁶ and R⁷ are each a hydrogen atom; a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof.
 2. The compound according to claim 1 or a pharmacologically acceptable salt thereof, wherein R⁴ is a methyl group.
 3. The compound according to claim 2 or a pharmacologically acceptable salt thereof, wherein X is a group of a formula ═N—CH₃.
 4. The compound according to claim 1, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol, or a pharmacologically acceptable salt thereof.
 5. The compound according to claim 1, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol, or a pharmacologically acceptable salt thereof.
 6. The compound according to claim 1, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol, or a pharmacologically acceptable salt thereof.
 7. The compound according to claim 1, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(4-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol.
 8. The compound according to claim 1, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol.
 9. The compound according to claim 1, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(4-methoxyphenyl)butanoyl]pyrrol-2-yl}butan-1-ol.
 10. The compound according to claim 1, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3-methylphenyl)butyl]pyrrol-2-yl}butan-1-ol.
 11. The compound according to claim 1, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol.
 12. The compound according to claim 1, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol.
 13. The compound according to claim 1, wherein said compound is 2-amino-2-methyl-4-{1methyl-5-[4-(3-triflouromethylphenyl)butyl]pyrrol-2-yl}butan-1-ol.
 14. The compound according to claim 1, wherein R¹, R² and R³ are each a hydrogen atom, R⁴ is a methyl group, n is 2 and Y—Z—R⁵ is —(O—(CH₂)₃-(4-F-phenyl).
 15. The compound according to claim 1, wherein the compound is selected from the group consisting of 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol; 2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol; 2-amino-2-methyl-4-{1-methyl-5-[4-(3-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol; 2-amino-2-methyl-4-{1-methyl-5-[4-(4-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol; 2-amino-2-methyl-4-{1-methyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol; 2-amino-2-methyl-4-{1-methyl-5-[4-(4-methoxyphenyl)butanoyl]pyrrol-2-yl}butan-1-ol; 2-amino-2-methyl-4-{1-methyl-5-[4-(3-methylphenyl)butyl]pyrrol-2-yl}butan-1-ol; 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol; 2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol; 2-amino-2-methyl-4-{1-methyl-5-[4-(3-triflouromethylphenyl)butyl]pyrrol-2-yl}butan-1-ol; and a compound of the formula (Ia), wherein R¹, R² and R³ are each a hydrogen atom, R⁴ is a methyl group, n is 2 and Y—Z—R⁵ is —CO—(CH₂)₃-(4-F-phenyl), or a pharmacologically acceptable salt thereof.
 16. The compound according to claim 4, wherein the configuration at the carbon atom to which the group of the formula —NR¹R² attaches is the R configuration, or a pharmacologically acceptable salt thereof.
 17. The compound according to claim 5, wherein the configuration at the carbon atom to which the group of the formula —NR¹R² attaches is the R configuration, or a pharmacologically acceptable salt thereof.
 18. The compound according to claim 6, wherein the configuration at the carbon atom to which the group of the formula —NR¹R² attaches is the R configuration, or a pharmacologically acceptable salt thereof.
 19. The compound according to claim 7, wherein the configuration at the carbon atom to which the group of the formula —NR¹R² attaches is the R configuration, or a pharmacologically acceptable salt thereof.
 20. The compound according to claim 8, wherein the configuration at the carbon atom to which the group of the formula —NR¹R² attaches is the R configuration, or a pharmacologically acceptable salt thereof.
 21. The compound according to claim 9, wherein the configuration at the carbon atom to which the group of the formula —NR¹R² attaches is the R configuration, or a pharmacologically acceptable salt thereof.
 22. The compound according to claim 10, wherein the configuration at the carbon atom to which the group of the formula —NR¹R² attaches is the R configuration, or a pharmacologically acceptable salt thereof.
 23. The compound according to claim 11, wherein the configuration at the carbon atom to which the group of the formula —NR¹R² attaches is the R configuration, or a pharmacologically acceptable salt thereof.
 24. The compound according to claim 12, wherein the configuration at the carbon atom to which the group of the formula —NR¹R² attaches is the R configuration, or a pharmacologically acceptable salt thereof.
 25. The compound according to claim 13, wherein the configuration at the carbon atom to which the group of the formula —NR¹R² attaches is the R configuration, or a pharmacologically acceptable salt thereof.
 26. The compound according to claim 14, wherein the configuration at the carbon atom to which the group of the formula —NR¹R² attaches is the R configuration, or a pharmacologically acceptable salt thereof.
 27. A pharmaceutical composition comprising as an active ingredient a compound, a pharmacologically acceptable salt thereof or a pharmacologically acceptable ester thereof according to any one of claims 1 to 26, in combination with a pharmacologically acceptable carrier.
 28. A method for the treatment of a disease selected from the group consisting of rheumatoid arthritis and psoriasis in a human in need thereof, which comprises administering to said human a pharmaceutically effective amount of a compound, a pharmacologically acceptable salt or a pharmacologically acceptable ester according to any one of claims 1 to
 26. 29. The method according to claim 28, wherein the disease is rheumatoid arthritis.
 30. The method according to claim 28, wherein the disease is psoriasis.
 31. A method for the treatment of a disease selected from the group consisting of rheumatoid arthritis and psoriasis in a mammal in need thereof comprising administering to said mammal a pharmaceutically effective amount of a compound according to any one of claims 1 to 26, a pharmacologically acceptable salt thereof or a pharmacologically acceptable ester thereof. 